|Year : 2017 | Volume
| Issue : 3 | Page : 143-151
Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury
Michael G Liska1, Ike dela Peña2
1 Center of Excellence for Aging and Brain Repair, Tampa, FL 33612, USA
2 Department of Pharmaceutical and Administrative Sciences, School of Pharmacy, College of Pharmacy, Loma Linda University, Loma Linda, CA, USA
|Date of Submission||05-Aug-2017|
|Date of Decision||31-Aug-2017|
|Date of Acceptance||05-Sep-2017|
|Date of Web Publication||12-Oct-2017|
Ike dela Peña
College of Pharmacy, Loma Linda University, Loma Linda, CA
Source of Support: None, Conflict of Interest: None
Traumatic brain injury (TBI) is now characterized as a progressive, degenerative disease and continues to stand as a prevalent cause of death and disability. The pathophysiology of TBI is complex, with a variety of secondary cell death pathways occurring which may persist chronically following the initial cerebral insult. Current therapeutic options for TBI are minimal, with surgical intervention or rehabilitation therapy existing as the only viable treatments. Considering the success of stem-cell therapies in various other neurological diseases, their use has been proposed as a potential potent therapy for patients suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with other therapies, providing an opportunity to overcome the inherent limitations of using a single therapeutic agent. Our research has verified this additive potential by demonstrating the efficacy of co-delivering human umbilical cord blood (hUCB) cells with granulocyte-colony stimulating factor (G-CSF) in a murine model of TBI, providing encouraging results which support the potential of this approach to treat patients suffering from TBI. These findings justify ongoing research toward uncovering the mechanisms which underlie the functional improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating its safe and effect transition into the clinic. This paper is a review article. Referred literature in this paper has been listed in the reference section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.
Keywords: Central nervous system disorders, granulocyte-colony stimulating factor, human umbilical cord blood, regenerative medicine, stem-cell therapy, traumatic brain injury
|How to cite this article:|
Liska MG, dela Peña I. Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury. Brain Circ 2017;3:143-51
|How to cite this URL:|
Liska MG, dela Peña I. Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury. Brain Circ [serial online] 2017 [cited 2020 Sep 26];3:143-51. Available from: http://www.braincirculation.org/text.asp?2017/3/3/143/216587
| Introduction|| |
Traumatic brain injury (TBI) – defined as a physical insult which damages brain tissue by exceeding the protective capacity of the cranium – has continued to persist as a public health concern. Approximately 3.5 million TBIs were reported in 2009 alone, with 2.1 million resulting in emergency room visits and 53,000 in death. Moreover, a dramatic increase in blast injuries has paralleled the rise of improvised explosive devices in current armed conflicts, causing TBI to become the “signature wound” for American troops. The severity of TBI can vary, ranging from a mild change in mental status to coma and induction of amnesia after the injury. (National Institute of Neurological Disorders and Stroke, National Institutes of Health). Mortality following TBI spans from 1% in mild TBI cases to upward of 30%–50% following severe brain injuries; mild TBI, however, constitutes the majority of TBI cases at 70%–80%.
Following the primary cerebral insult, complex pathological sequelae propagate neural death which may persist days, months, or even years., The initial cause of TBI can be focal, such as from a penetrating head wound, or diffuse, such as from a blast-induced insult. The secondary injuries stem from this primary trauma and result in multiple pathological cascades including excitotoxicity, hypoxia/ischemia, mitochondrial dysfunction, neuroinflammation, oxidative stress, and cerebral edema, which all contribute to the persistence of neurodegeneration and chronic functional deficits.,,,,,, These secondary effects are often the most devastating and influential component of TBI progression, responsible for the delayed mortality and symptom development seen both in patients and animal models of TBI.,,, In search of novel therapeutics, halting the progression of these secondary pathologies presents an appealing target.
Beyond the physiopathology of the primary and secondary brain injury, TBI in humans is often associated with broader complications such as hydrocephalus, posttraumatic ventricular enlargement, seizures, nerve and vascular injuries, and polytrauma (National Institute of Neurological Disorders and Stroke, National Institutes of Health). Moreover, high-functioning impairments in cognition, communication, sensory–motor integration, and mental status (i.e., anxiety, aggression, and depression) may accompany chronic human TBI.,,, TBI survivors have also been observed to present with symptoms which mimic neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), dementia pugilistica, and posttraumatic dementia.,,,,
A general lack of awareness as to the prevalence of mild TBI has exacerbated this public health concern, with patients often forgoing treatment until symptoms begin worsening. Even when seeking treatment, TBI patients' therapeutic opportunities are extremely limited. In severe cases, surgical intervention may be beneficial in the repair or excision of damaged vasculature or tissue, while the various other symptoms – such as seizures, headaches, chronic pain, behavioral abnormalities, and depression – are relegated to management through prescription drugs and rehabilitation therapy.,,,,,, Unfortunately, these treatment plans fail to prevent or reverse the underlying pathology. Thus, a substantial medical gap exists in the availability of TBI therapies which effectively treat the progressing secondary injury mechanisms and facilitate lasting functional recovery.
| Umbilical Cord Blood Cells and a Viable Donor Source for Transplantation in Traumatic Brain Injury|| |
By attenuating the toxic cell damage and detrimental edema which accompany TBI, neuroprotective pharmaceuticals and nontraditional agents aim to inhibit the development of secondary brain injuries. Completed clinical trials investigating the safety and efficacy of select neuroprotective agents which exhibited preclinical success including glutamate inhibitors, nimodipine, magnesium sulfate, scavenging agents, and competitive N-methyl-D-aspartate receptor antagonists have failed to exhibit efficacy in TBI patients.,,,, Testifying to the complexity of human TBI pathophysiology, these failed therapies indicate the need for new and improved treatment modalities.
In light of the extended therapeutic time window associated with chronic TBI, treatment strategies have been tailored to pursue chronic phase neuroregenerative efforts as opposed to targeting the narrow neuroprotective window of acute TBI., the forefront of regenerative medicine has been stem cell-based therapies, having displayed promising applications in many neurological disorders such as TBI and having reached limited clinical trials.,,,,,, A rigorous analysis of the safety, efficacy, and mechanisms of action has been critical to translating the use of stem cells for the treatment of neurological ailments. This has included extensive research into a multitude of transplantable cell types including fetal stem cells, cancer-derived neuron-like cells, embryonic stem cells, induced pluripotent stem cells, and adult stem cells, such as umbilical cord blood, bone marrow (BM) stromal cells, and amnion cells, among others.,,,,,,,, Of particular interest has been adult stem cell donor sources as they evade the ethical, logistical, and oncogenic concerns which plague transplantation of embryonal or fetal-derived stem cells.
Many laboratories, including our own, have gauged the clinical value of human umbilical cord blood (hUCB)-derived cells for the treatment of neurological disorders such as cerebral palsy, stroke, PD, and Huntington's disease., These investigations have resulted in limited clinical trials of hUCB cells in cerebral palsy, stroke, and metabolic disorders.,,, The advantages of hUCB cell transplantation are a low immunogenicity, an ability to retain effectiveness after years of cryopreservation, ease of harvesting, ease of in vitro expansion, stemness potency, and successful history within the clinic for hematopoietic disorders. Experimental models of TBI have responded favorably to hUCB treatment; transplantation of the mononuclear fraction of hUCB resulted in neuroprotective effects through reduced inflammation, heightened neurogenesis, and a rescue of functional outcomes.,, Moreover, mesenchymal stem cells (MSCs) derived from hUCB conferred neuroprotective and neuroregenerative benefits through improved angiogenesis and vasculogenesis.,, The transition of hUCB cell transplantations for the treatment of TBI in the clinic will demand extensive basic science and translational research initiatives to uncover the intricate mechanisms of action, as well as the ideal timing, dosage, and route of administration. Furthermore, establishing the most appropriate and reproducible source of these cells will be essential for quality assurance, quality control, and reproducibility of experimental outcome measures.
Despite inflammation and the harsh postinjury microenvironment being unconducive to long-term graft survival,, a robust functional recovery is still attainable in animal models through bystander effects; achieving significant recovery in the clinic, however, will likely necessitate dampening the harsh microenvironment and making it more receptive to stem cell transplant survival. Indeed, rendering the harsh postinjury microenvironment more amenable to stem cells through adjunctive agents may enhance their effectiveness and facilitate their advancement into the clinic for the treatment of TBI.
| An Introduction to Granulocyte-Colony Stimulating Factor|| |
First discovered in the mid-1960s, granulocyte-colony stimulating factor (G-CSF) is a hematopoietic glycoprotein growth factor released from various cell types including endothelial cells, activated macrophages, and fibroblasts., Initially, G-CSF was characterized to have roles in regulating differentiation, proliferation, survival, and function of neutrophil granulocyte progenitor cells and mature neutrophils., G-CSF is now known to have a more broad set of functions; these are inducing growth of primarily neutrophilic granulocyte colonies in a colony-forming units-granulocyte macrophage assay, enhancing production of the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine binding to mature neutrophils, and well-characterized regulation of the proliferation and differentiation of granulocyte precursor cells.,, In addition, experiments utilizing G-CSF knockout mice revealed the role which this growth factor has in maintaining appropriate levels of circulating neutrophils in baseline myelopoiesis.,
Specific cellular queues trigger the production and release of G-CSF in the BM, whereby it can proceed to bind specialized receptors such as the canonical G-CSF receptor in a variety of cell types including hematopoietic progenitor cells, monocytes, platelets, neurons, endothelial cells, and small-cell lung cancer cells.,,,, Upon activation of these receptors, signaling cascades are initiated which have been implicated in cell proliferation, anti-inflammatory processes, and anti-apoptotic pathways as well as stem cell mobilization toward sites of injury.,,,,,,,,, Furthermore, G-CSF has been implicated in brain function and recovery due to its ability to bypass the blood–brain barrier (BBB) and promote neural recovery,,, indicating its candidacy as a possible treatment for neurodegenerative diseases.
Monotherapeutic applications of granulocyte-colony stimulating factor
With neutropenia or febrile neutropenia potentially resulting from myelosuppressive or myeloablative chemotherapies, G-CSF has been approved by the Food and Drug Administration (FDA) for the treatment of appropriate cancer patients. Clinic trials of G-CSF for small-cell lung cancer patients showed that treatment reduced the occurrence of infection, need for antibiotics, and decreased hospitalization rates for patients., Other randomized, controlled clinical trials have shown a reduced duration of neutropenia, decreased hospitalization, and reduced antibiotic treatment in lymphoma patients subjected to myeloablative chemotherapy and autologous BM transplantation. Interestingly, stem cell transplantation can generate prolonged neutropenia. In patients with lymphoma, injection of G-CSF 24 h after autologous marrow transplantation resulted in quicker recovery of granulocyte count. Accelerated recovery of neutrophil levels has also been reported in other studies of G-CSF-treated patients ailed with lymphoma, leukemia, and germ cell tumors., Finally, G-CSF has been demonstrated as valuable for patients undergoing consolidation therapy as well as other idiopathic, congenital, or cyclic neutropenic conditions.,,
Early clinical trials in cancer patients receiving G-CSF revealed that a 100-fold increase in circulating colony-forming progenitor cells accompanied treatment. These findings initiated a quest to determine if peripheral blood progenitor cells (PBPC) mobilized by G-CSF could rehabilitate hematopoiesis or if G-CSF could mobilize granulocytes in healthy donors. Indeed, in poor-prognosis nonmyeloid malignancy patients, it was observed that G-CSF-mobilized PBPC treatment stimulated platelet recovery. It has also been shown that G-CSF-mobilized PBPCs can be safely and effectively harvested from donors. Studies utilizing G-CSF-mobilized PBPCs (as opposed to BM stem cells) in allogeneic transplantation have prompted the clinical use of G-CSF for mobilization and collection of PBPC for disease treatment. The long history of safe and effective G-CSF use in the clinic makes it an appealing option from a therapy-development standpoint as entry of repurposed drugs into the clinic is typically expedited.
Further indications for the use of granulocyte-colony stimulating factor
The ability of G-CSF to mobilize BM stem cells into circulation has been the basis for a number of investigation into this recombinant protein's potential regenerative benefits in myocardial infarction. A number of clinical trials of G-CSF for cardiac repair which have inconclusive with their reports of efficacy are included in these investigations. Still, valuable knowledge was attained from these studies regarding the therapeutic mechanisms of G-CSF and relevant signaling pathways which modulate homing and prompt engraftment.
With G-CSF able to penetrate the BBB and bind to neural receptors, its potential in the treatment of central nervous system disorders is significant. G-CSF has been demonstrated to incite a number of neuroprotective pathways which indicate its relevance in treating neurodegenerative diseases; among these, effects are mobilizing peripheral stem cells, stimulating neuronal lineage differentiation of endogenous stem cells, promoting angiogenesis, and dampening inflammation, all acting in concert to reduce apoptosis.,,, Stroke, in particular, has been revealed as highly amenable to G-CSF therapy, with properly dosed treatments resulting in increased CD34+ cells, reduced glutamate excitotoxicity, altered apoptotic pathways,, reduced edema and interleukin-1 expression, and decreased infarct size. This promising preclinical evidence has precipitated clinical studies into the safety and efficacy of G-CSF treatment in ischemic stroke patients.,, Positive indications have also been derived from clinical trials of G-CSF in AD, with appropriate dosages being well-tolerated and improving performance in hippocampal-dependent cognitive tests. The potential of G-CSF to induce neuroregeneration – within the central nervous and peripheral nervous system – has been proposed. Indeed, studies have shown G-CSF to promote function recovery from spinal cord injury (SCI) by increasing neuron survival and oligodendrocyte protection., The safety and feasibility of G-CSF treatment for SCI was demonstrated in phase I/IIa clinical trials, signifying the promise of G-CSF to confer functional benefits in acute SCI patients.
With discrepant results being produced in studies of G-CSF for the treatment of experimental TBI – some reporting improved histological markers and behavioral performance, others finding minimal effect on neurological outcomes – the merit of this protein as a stand-alone therapy for TBI is inconclusive.,, Despite the inconsistent efficacy results, a clinical trial has been initiated for G-CSF in TBI patients on the basis of its solid safety profile and positive indications in both ischemic stroke and AD.,,,, The multitude of positive findings for the use of G-CSF in various neurological conditions warrants ongoing investigation into the potential applications of G-CSF in TBI treatment.
| Granulocyte-Colony Stimulating Factor as an Adjunctive Option|| |
Different mobilizing agents may promote the dissemination of BM stem cells with different phenotypic profiles and biological characteristics; thus, G-CSF has been used adjunctively with other mobilization compounds agents, such as stem cell factor (SCF), to enhance and optimize the mobilization of stem cells., Working synergistically, co-administration of G-CSF and SCF resulted in a 250-fold increase in circulating pluripotent hematopoietic stem cells. Consistent with these findings, myocardial infarct studies have reported that such combination therapy resulted in improved left ventricular function, reduced mortality and infarct size, and improved homing of BM stem cells to the affected myocardium, resulting in the formation of new cardiomyocytes. Chronic stroke studies revealed the adjunctive therapy of G-CSF and SCF augment functional recovery better than either treatment alone, citing increased neurogenesis, angiogenesis, and indirect neural network promotion as the mechanisms underlying the improvements.
Similarly, co-administration of G-CSF and cytokine fms-like tyrosine kinase 3 (Flt3), demonstrated therapeutic effects in models of SCI and acute myocardial infarction which were more effective than either single-agent treatment.,, An extended period of mobilized BM cells was associated with the improvements in tissue regeneration, morphological, and behavioral measurements observed following the adjunctive treatment., Further, when combined with transplantation of the mononuclear fraction of BM cells, G-CSF treatment produced combinatorial effects in a mouse model of ischemic stroke, potentially through enhanced proliferation and differentiation of BM stem cells which, in turn, promoted regeneration.
The efficacy of G-CSF alone or in combination with BM-MSC was investigated after experimental stroke in aged rats. Despite significant upregulation of angiogenesis in the infarct core and penumbral region, the neuroprotective effects of the combination therapy were less pronounced than those afforded by G-CSF alone. These findings, however, are in agreeance with previous studies which described the pro-survival properties of G-CSF in aged rats. Thus, additional studies into the interactions between G-CSF and stem cells are warranted to better understand the lack of synergism reported in this study.
In a model of spinal cord transection, BM-MSC transplantation with G-CSF did displayed synergistic effects on recovery, attributed largely to increased proliferation and differentiation of BM stem cells, and subsequent neural regeneration. The additive effects may have also been due to increased neurogenesis of both the endogenous neurons and neural lineage-committed transplant cells in the transverse SCI. Using G-CSF adjunctively with other therapeutic agents has been employed with pharmacotherapies, erythropoietin, amniotic membrane wrappings, and other tools in experimental neurological disease models. When compared to single-agent interventions, the majority of these investigations report synergism through combination therapies, supporting the concept of heightened therapeutic potency with G-CSF as an adjunctive therapy.
Granulocyte-colony stimulating factor and human umbilical cord blood cell transplantation – evidence toward clinical translation
Based on the previous successes of G-CSF as both an adjunctive and stand-alone therapy for neurological disorders – and in light of the discordant findings with G-CSF in TBI models – we investigated the merit of a combinatorial approach in treating the controlled cortical impact model of TBI with transplantation of hUCB and co-administration of G-CSF. Our study demonstrated greater therapeutic benefits offered through combination therapy of hUCB and G-CSF than either agent alone. Moreover, these functional improvements prevailed for a longer period than in the monotherapy groups. These results attest to the ability of complementary brain repair processes not only to afford functional recovery but also to potentially sustain these benefits. Secretions of hUCB grafts, G-CSF-mobilized endogenous stem cells, and possible graft-host interactions may have exerted cooperative regenerative mechanisms which resulted in neurological recovery surpassing that afforded by G-CSF or hUCB treatments alone.,
Considering our group's long-standing interest in the inflammatory basis of neurodegeneration, we utilized MHC-II staining of activated microglia to determine the effects which G-CSF + hUCB combination therapy exerted on TBI-induced neuroinflammation. In line with the functional improvements we noted, the combination therapy group displayed a reduction in the TBI-induced upregulation of MHC-II microglia in the cortex, striatum, subventricular zone (SVZ), dentate gyrus (DG) of the hippocampus, corpus callosum, fornix, thalamus, and cerebral peduncle compared to either stand-alone treatment. Preclinical evidence has demonstrated the ability of hUCB transplantation to induce neurogenesis, angiogenesis, and attenuate neuroinflammation in models of TBI as well as stroke and aging.,, G-CSF treatment has similarly been noted to promote neurogenesis in TBI models. Our results support the notion that these two treatment modalities can combine synergistically, encouraging neurogenesis in the DG and SVZ, dampening neuroinflammation, and preserving hippocampal cells to confer functional benefits which surpass that of either monotherapy.,
Complementary interactions between hUCB and G-CSF likely facilitated the aforementioned widespread effects seen in the TBI brain. G-CSF has been shown to mobilize stem cells which can infiltrate damaged brain tissue and promote repair,, while also crossing the BBB itself where it can interact with neurons and glial cells to downregulate pro-inflammatory mediators and increase neurogenesis.,, Furthermore, G-CSF may encourage the hUCB cells to maintain stemness and even promote neural lineage commitment., Combination treatment of G-CSF and SCF was shown to promote senescence and neural lineage commitment of hematopoietic stem cells, possibly through neurogenin-1 activation. Simultaneously, the mobilized BM stem cells can exert bystander effects by the way of paracrine signaling/immunomodulation through cytokines, chemokines, and trophic factors.,,, These diverse and cooperative mechanisms likely underlie the anti-inflammatory, neurogenic, and pro-survival effects seen in cases treated with G-CSF and hUCB.
| Conclusion|| |
Shifting the paradigm of TBI from an acute event to a progressive, neurodegenerative disease has paved the way for novel therapeutic opportunities which target this extended pathological window. These opportunities are welcomed as treatment options for TBI are practically nonexistent, with patient treatment relegated to symptom management and rehabilitation therapy. Stem cells have been proposed as a biological agent which may effectively target the progressive degeneration of chronic TBI, largely due to promising preclinical data in experimental models of TBI and various neurological disorders. Importantly, it is becoming increasingly evident that optimizing stem-cell therapy may require adjunctive therapies which work synergistically with the stem cells to promote significant and sustained functional recovery. We have provided experimental evidence that one such adjunctive option – G-CSF co-administered with hUCB cells – is a viable and effective modality and may present a means of overcoming the innate limitations that exist in monotherapy with either therapeutic. This evidence warrants further investigation into G-CSF + hUCB combination therapy, as well as other promising combinations, in an attempt to demonstrate their safety and efficacy, eventually propelling these regenerative therapeutic approaches into the clinic for the treatment of TBI.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Corrigan JD, Selassie AW, Orman JA. The epidemiology of traumatic brain injury. J Head Trauma Rehabil 2010;25:72-80.
Cuthbert JP, Harrison-Felix C, Corrigan JD, Kreider S, Bell JM, Coronado VG, et al.
Epidemiology of adults receiving acute inpatient rehabilitation for a primary diagnosis of traumatic brain injury in the United States. J Head Trauma Rehabil 2015;30:122-35.
Thurman D, Guerrero J. Trends in hospitalization associated with traumatic brain injury. JAMA 1999;282:954-7.
Arciniegas DB, Anderson CA, Topkoff J, McAllister TW. Mild traumatic brain injury: A neuropsychiatric approach to diagnosis, evaluation, and treatment. Neuropsychiatr Dis Treat 2005;1:311-27.
McAllister TW. Neurobiological consequences of traumatic brain injury. Dialogues Clin Neurosci 2011;13:287-300.
Gennarelli TA. Mechanisms of brain injury. J Emerg Med 1993;11 Suppl 1:5-11.
Lee B, Newberg A. Neuroimaging in traumatic brain imaging. NeuroRX 2005;2:372-83.
Gao Y, Xu S, Cui Z, Zhang M, Lin Y, Cai L, et al.
Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury. J Neurochem 2015;134:340-53.
Rodríguez-Rodríguez A, Egea-Guerrero JJ, Murillo-Cabezas F, Carrillo-Vico A. Oxidative stress in traumatic brain injury. Curr Med Chem 2014;21:1201-11.
Hernandez-Ontiveros DG, Tajiri N, Acosta S, Giunta B, Tan J, Borlongan CV, et al.
Microglia activation as a biomarker for traumatic brain injury. Front Neurol 2013;4:30.
Maas AI, Stocchetti N, Bullock R. Moderate and severe traumatic brain injury in adults. Lancet Neurol 2008;7:728-41.
Zhang YB, Li SX, Chen XP, Yang L, Zhang YG, Liu R, et al.
Autophagy is activated and might protect neurons from degeneration after traumatic brain injury. Neurosci Bull 2008;24:143-9.
Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth 2007;99:4-9.
Werner JK, Stevens RD. Traumatic brain injury: Recent advances in plasticity and regeneration. Curr Opin Neurol 2015;28:565-73.
Reilly PL. Brain injury: The pathophysiology of the first hours.'Talk and die revisited'. J Clin Neurosci 2001;8:398-403.
Graham DI, McIntosh TK, Maxwell WL, Nicoll JA. Recent advances in neurotrauma. J Neuropathol Exp Neurol 2000;59:641-51.
Sandry J, DeLuca J, Chiaravalloti N. Working memory capacity links cognitive reserve with long-term memory in moderate to severe TBI: A translational approach. J Neurol 2015;262:59-64.
Wong JC, Hazrati LN. Parkinson's disease, parkinsonism, and traumatic brain injury. Crit Rev Clin Lab Sci 2013;50:103-6.
Wong D, Dahm J, Ponsford J. Factor structure of the depression anxiety stress scales in individuals with traumatic brain injury. Brain Inj 2013;27:1377-82.
Azouvi P, Vallat-Azouvi C, Belmont A. Cognitive deficits after traumatic coma. Prog Brain Res 2009;177:89-110.
Esopenko C, Levine B. Aging, neurodegenerative disease, and traumatic brain injury: The role of neuroimaging. J Neurotrauma 2015;32:209-20.
Kokjohn TA, Maarouf CL, Daugs ID, Hunter JM, Whiteside CM, Malek-Ahmadi M, et al.
Neurochemical profile of dementia pugilistica. J Neurotrauma 2013;30:981-97.
Nemetz PN, Leibson C, Naessens JM, Beard M, Kokmen E, Annegers JF, et al.
Traumatic brain injury and time to onset of Alzheimer's disease: A population-based study. Am J Epidemiol 1999;149:32-40.
Kochanek PM, Jackson TC, Ferguson NM, Carlson SW, Simon DW, Brockman EC, et al.
Emerging therapies in traumatic brain injury. Semin Neurol 2015;35:83-100.
Twamley EW, Jak AJ, Delis DC, Bondi MW, Lohr JB. Cognitive symptom management and rehabilitation therapy (CogSMART) for veterans with traumatic brain injury: Pilot randomized controlled trial. J Rehabil Res Dev 2014;51:59-70.
Brasure M, Lamberty GJ, Sayer NA, Nelson NW, Macdonald R, Ouellette J, et al.
Participation after multidisciplinary rehabilitation for moderate to severe traumatic brain injury in adults: A systematic review. Arch Phys Med Rehabil 2013;94:1398-420.
Giustini A, Pistarini C, Pisoni C. Traumatic and nontraumatic brain injury. Handb Clin Neurol 2013;110:401-9.
Lu J, Gary KW, Neimeier JP, Ward J, Lapane KL. Randomized controlled trials in adult traumatic brain injury. Brain Inj 2012;26:1523-48.
Walker PA, Harting MT, Baumgartner JE, Fletcher S, Strobel N, Cox CS Jr., et al.
Modern approaches to pediatric brain injury therapy. J Trauma 2009;67:S120-7.
Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care, AANS/CNS, Bratton SL, Chestnut RM, et al.
Guidelines for the management of severe traumatic brain injury. IX. Cerebral perfusion thresholds. J Neurotrauma 2007;24 Suppl 1:S59-64.
Temkin NR, Anderson GD, Winn HR, Ellenbogen RG, Britz GW, Schuster J, et al.
Magnesium sulfate for neuroprotection after traumatic brain injury: A randomised controlled trial. Lancet Neurol 2007;6:29-38.
Narayan RK, Michel ME, Ansell B, Baethmann A, Biegon A, Bracken MB, et al.
Clinical trials in head injury. J Neurotrauma 2002;19:503-57.
Marshall LF. Head injury: Recent past, present, and future. Neurosurgery 2000;47:546-61.
Tajiri N, Acosta SA, Shahaduzzaman M, Ishikawa H, Shinozuka K, Pabon M, et al.
Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: Cell graft biodistribution and soluble factors in young and aged rats. J Neurosci 2014;34:313-26.
Mueller BK, Mueller R, Schoemaker H. Stimulating neuroregeneration as a therapeutic drug approach for traumatic brain injury. Br J Pharmacol 2009;157:675-85.
Stonesifer C, Corey S, Ghanekar S, Diamandis Z, Acosta SA, Borlongan CV, et al.
Stem cell therapy for abrogating stroke-induced neuroinflammation and relevant secondary cell death mechanisms. Prog Neurobiol 2017. pii: S0301-0082(17) 30082-5.
Huang H, Chen L, Sanberg PR. Clinical achievements, obstacles, falsehoods, and future directions of cell-based neurorestoratology. Cell Transplant 2012;21 Suppl 1:S3-11.
Yang M, Wei X, Li J, Heine LA, Rosenwasser R, Iacovitti L, et al.
Changes in host blood factors and brain glia accompanying the functional recovery after systemic administration of bone marrow stem cells in ischemic stroke rats. Cell Transplant 2010;19:1073-84.
Liu YP, Lang BT, Baskaya MK, Dempsey RJ, Vemuganti R. The potential of neural stem cells to repair stroke-induced brain damage. Acta Neuropathol 2009;117:469-80.
Mahmood A, Lu D, Lu M, Chopp M. Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery 2003;53:697-702.
Lindvall O, Brundin P, Widner H, Rehncrona S, Gustavii B, Frackowiak R, et al.
Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease. Science 1990;247:574-7.
Sanchez-Ramos J, Cimino C, Avila R, Rowe A, Chen R, Whelan G, et al.
Pilot study of granulocyte-colony stimulating factor for treatment of Alzheimer's disease. J Alzheimers Dis 2012;31:843-55.
Chen SJ, Chang CM, Tsai SK, Chang YL, Chou SJ, Huang SS, et al.
Functional improvement of focal cerebral ischemia injury by subdural transplantation of induced pluripotent stem cells with fibrin glue. Stem Cells Dev 2010;19:1757-67.
Sakowitz OW, Schardt C, Neher M, Stover JF, Unterberg AW, Kiening KL, et al.
Granulocyte colony-stimulating factor does not affect contusion size, brain edema or cerebrospinal fluid glutamate concentrations in rats following controlled cortical impact. Acta Neurochir Suppl 2006;96:139-43.
Mahmood A, Lu D, Qu C, Goussev A, Chopp M. Long-term recovery after bone marrow stromal cell treatment of traumatic brain injury in rats. J Neurosurg 2006;104:272-7.
Newman MB, Misiuta I, Willing AE, Zigova T, Karl RC, Borlongan CV, et al.
Tumorigenicity issues of embryonic carcinoma-derived stem cells: Relevance to surgical trials using NT2 and hNT neural cells. Stem Cells Dev 2005;14:29-43.
Newman MB, Davis CD, Kuzmin-Nichols N, Sanberg PR. Human umbilical cord blood (HUCB) cells for central nervous system repair. Neurotox Res 2003;5:355-68.
Sanberg PR, Eve DJ, Metcalf C, Borlongan CV. Advantages and challenges of alternative sources of adult-derived stem cells for brain repair in stroke. Prog Brain Res 2012;201:99-117.
Acosta SA, Franzese N, Staples M, Weinbren NL, Babilonia M, Patel J, et al.
Human umbilical cord blood for transplantation therapy in myocardial infarction. J Stem Cell Res Ther 2013; Suppl 4. pii: S4-005.
Sanberg PR, Willing AE, Garbuzova-Davis S, Saporta S, Liu G, Sanberg CD, et al.
Umbilical cord blood-derived stem cells and brain repair. Ann N
Y Acad Sci 2005;1049:67-83.
Verina T, Fatemi A, Johnston MV, Comi AM. Pluripotent possibilities: Human umbilical cord blood cell treatment after neonatal brain injury. Pediatr Neurol 2013;48:346-54.
Ilic D, Miere C, Lazic E. Umbilical cord blood stem cells: Clinical trials in non-hematological disorders. Br Med Bull 2012;102:43-57.
Copeland N, Harris D, Gaballa MA. Human umbilical cord blood stem cells, myocardial infarction and stroke. Clin Med (Lond) 2009;9:342-5.
Biazar E. Use of umbilical cord and cord blood-derived stem cells for tissue repair and regeneration. Expert Opin Biol Ther 2014;14:301-10.
Pimentel-Coelho PM, Rosado-de-Castro PH, da Fonseca LM, Mendez-Otero R. Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic-ischemic encephalopathy. Pediatr Res 2012;71:464-73.
Boltze J, Reich DM, Hau S, Reymann KG, Strassburger M, Lobsien D, et al.
Assessment of neuroprotective effects of human umbilical cord blood mononuclear cell subpopulations in vitro
and in vivo
. Cell Transplant 2012;21:723-37.
Henning RJ, Shariff M, Eadula U, Alvarado F, Vasko M, Sanberg PR, et al.
Human cord blood mononuclear cells decrease cytokines and inflammatory cells in acute myocardial infarction. Stem Cells Dev 2008;17:1207-19.
Li T, Ma Q, Ning M, Zhao Y, Hou Y. Cotransplantation of human umbilical cord-derived mesenchymal stem cells and umbilical cord blood-derived CD34+ cells in a rabbit model of myocardial infarction. Mol Cell Biochem 2014;387:91-100.
Lee EJ, Choi EK, Kang SK, Kim GH, Park JY, Kang HJ, et al.
N-cadherin determines individual variations in the therapeutic efficacy of human umbilical cord blood-derived mesenchymal stem cells in a rat model of myocardial infarction. Mol Ther 2012;20:155-67.
Woodcock T, Morganti-Kossmann MC. The role of markers of inflammation in traumatic brain injury. Front Neurol 2013;4:18.
Kumar A, Loane DJ. Neuroinflammation after traumatic brain injury: Opportunities for therapeutic intervention. Brain Behav Immun 2012;26:1191-201.
Metcalf D. The colony-stimulating factors and cancer. Nat Rev Cancer 2010;10:425-34.
Solaroglu I, Jadhav V, Zhang JH. Neuroprotective effect of granulocyte-colony stimulating factor. Front Biosci 2007;12:712-24.
Lieschke GJ, Grail D, Hodgson G, Metcalf D, Stanley E, Cheers C, et al.
Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 1994;84:1737-46.
Platzer E, Welte K, Gabrilove JL, Lu L, Harris P, Mertelsmann R, et al.
Biological activities of a human pluripotent hemopoietic colony stimulating factor on normal and leukemic cells. J Exp Med 1985;162:1788-801.
Morikawa K, Morikawa S, Nakamura M, Miyawaki T. Characterization of granulocyte colony-stimulating factor receptor expressed on human lymphocytes. Br J Haematol 2002;118:296-304.
Shimoda K, Feng J, Murakami H, Nagata S, Watling D, Rogers NC, et al.
Jak1 plays an essential role for receptor phosphorylation and stat activation in response to granulocyte colony-stimulating factor. Blood 1997;90:597-604.
Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991;78:2791-808.
Hanazono Y, Hosoi T, Kuwaki T, Matsuki S, Miyazono K, Miyagawa K, et al.
Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils. Exp Hematol 1990;18:1097-103.
Basu S, Dunn A, Ward A. G-CSF: Function and modes of action (Review). Int J Mol Med 2002;10:3-10.
Stachura DL, Svoboda O, Campbell CA, Espín-Palazón R, Lau RP, Zon LI, et al.
The zebrafish granulocyte colony-stimulating factors (Gcsfs): 2 paralogous cytokines and their roles in hematopoietic development and maintenance. Blood 2013;122:3918-28.
Schneider A, Krüger C, Steigleder T, Weber D, Pitzer C, Laage R, et al.
The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis. J Clin Invest 2005;115:2083-98.
Ward AC, Loeb DM, Soede-Bobok AA, Touw IP, Friedman AD. Regulation of granulopoiesis by transcription factors and cytokine signals. Leukemia 2000;14:973-90.
Dong F, Larner AC. Activation of akt kinase by granulocyte colony-stimulating factor (G-CSF): Evidence for the role of a tyrosine kinase activity distinct from the janus kinases. Blood 2000;95:1656-62.
Hunter MG, Avalos BR. Phosphatidylinositol 3'-kinase and SH2-containing inositol phosphatase (SHIP) are recruited by distinct positive and negative growth-regulatory domains in the granulocyte colony-stimulating factor receptor. J Immunol 1998;160:4979-87.
Tian SS, Lamb P, Seidel HM, Stein RB, Rosen J. Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood 1994;84:1760-4.
Shimoda K, Okamura S, Harada N, Kondo S, Okamura T, Niho Y, et al.
Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 1993;91:1310-3.
Minnerup J, Sevimli S, Schäbitz WR. Granulocyte-colony stimulating factor for stroke treatment: Mechanisms of action and efficacy in preclinical studies. Exp Transl Stroke Med 2009;1:2.
Diederich K, Sevimli S, Dörr H, Kösters E, Hoppen M, Lewejohann L, et al.
The role of granulocyte-colony stimulating factor (G-CSF) in the healthy brain: A characterization of G-CSF-deficient mice. J Neurosci 2009;29:11572-81.
Schneider A, Kuhn HG, Schäbitz WR. A role for G-CSF (granulocyte-colony stimulating factor) in the central nervous system. Cell Cycle 2005;4:1753-7.
Xiao BG, Lu CZ, Link H. Cell biology and clinical promise of G-CSF: Immunomodulation and neuroprotection. J Cell Mol Med 2007;11:1272-90.
Aliper AM, Frieden-Korovkina VP, Buzdin A, Roumiantsev SA, Zhavoronkov A. A role for G-CSF and GM-CSF in nonmyeloid cancers. Cancer Med 2014;3:737-46.
Crawford J, Ozer H, Stoller R, Johnson D, Lyman G, Tabbara I, et al.
Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Engl J Med 1991;325:164-70.
Bronchud MH, Scarffe JH, Thatcher N, Crowther D, Souza LM, Alton NK, et al.
Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer 1987;56:809-13.
Lemoli RM, Rosti G, Visani G, Gherlinzoni F, Miggiano MC, Fortuna A, et al.
Concomitant and sequential administration of recombinant human granulocyte colony-stimulating factor and recombinant human interleukin-3 to accelerate hematopoietic recovery after autologous bone marrow transplantation for malignant lymphoma. J Clin Oncol 1996;14:3018-25.
Rüping MJ, Vehreschild JJ, Cornely OA. Patients at high risk of invasive fungal infections: When and how to treat. Drugs 2008;68:1941-62.
Taylor KM, Jagannath S, Spitzer G, Spinolo JA, Tucker SL, Fogel B, et al.
Recombinant human granulocyte colony-stimulating factor hastens granulocyte recovery after high-dose chemotherapy and autologous bone marrow transplantation in hodgkin's disease. J Clin Oncol 1989;7:1791-9.
Gorin NC, Isnard F, Garderet L, Ikhlef S, Corm S, Quesnel B, et al.
Administration of alemtuzumab and G-CSF to adults with relapsed or refractory acute lymphoblastic leukemia: Results of a phase II study. Eur J Haematol 2013;91:315-21.
Sheridan WP, Morstyn G, Wolf M, Dodds A, Lusk J, Maher D, et al.
Granulocyte colony-stimulating factor and neutrophil recovery after high-dose chemotherapy and autologous bone marrow transplantation. Lancet 1989;2:891-5.
Beekman R, Valkhof MG, Sanders MA, van Strien PM, Haanstra JR, Broeders L, et al.
Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. Blood 2012;119:5071-7.
Globus MY, Alonso O, Dietrich WD, Busto R, Ginsberg MD. Glutamate release and free radical production following brain injury: Effects of posttraumatic hypothermia. J Neurochem 1995;65:1704-11.
Dale DC, Bonilla MA, Davis MW, Nakanishi AM, Hammond WP, Kurtzberg J, et al.
A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 1993;81:2496-502.
Dührsen U, Villeval JL, Boyd J, Kannourakis G, Morstyn G, Metcalf D, et al.
Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients. Blood 1988;72:2074-81.
DeLuca E, Sheridan WP, Watson D, Szer J, Begley CG. Prior chemotherapy does not prevent effective mobilisation by G-CSF of peripheral blood progenitor cells. Br J Cancer 1992;66:893-9.
Sheridan WP, Begley CG, Juttner CA, Szer J, To LB, Maher D, et al.
Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 1992;339:640-4.
Hölig K. G-CSF in healthy allogeneic stem cell donors. Transfus Med Hemother 2013;40:225-35.
Shim W, Mehta A, Lim SY, Zhang G, Lim CH, Chua T, et al.
G-CSF for stem cell therapy in acute myocardial infarction: Friend or foe? Cardiovasc Res 2011;89:20-30.
Balseanu AT, Buga AM, Catalin B, Wagner DC, Boltze J, Zagrean AM, et al.
Multimodal approaches for regenerative stroke therapies: Combination of granulocyte colony-stimulating factor with bone marrow mesenchymal stem cells is not superior to G-CSF alone. Front Aging Neurosci 2014;6:130.
Solaroglu I, Cahill J, Tsubokawa T, Beskonakli E, Zhang JH. Granulocyte colony-stimulating factor protects the brain against experimental stroke via inhibition of apoptosis and inflammation. Neurol Res 2009;31:167-72.
Solaroglu I, Tsubokawa T, Cahill J, Zhang JH. Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat. Neuroscience 2006;143:965-74.
Meuer K, Pitzer C, Teismann P, Krüger C, Göricke B, Laage R, et al.
Granulocyte-colony stimulating factor is neuroprotective in a model of Parkinson's disease. J Neurochem 2006;97:675-86.
Komine-Kobayashi M, Zhang N, Liu M, Tanaka R, Hara H, Osaka A, et al.
Neuroprotective effect of recombinant human granulocyte colony-stimulating factor in transient focal ischemia of mice. J Cereb Blood Flow Metab 2006;26:402-13.
Pan C, Gupta A, Prentice H, Wu JY. Protection of taurine and granulocyte colony-stimulating factor against excitotoxicity induced by glutamate in primary cortical neurons. J Biomed Sci 2010;17 Suppl 1:S18.
Shyu WC, Lin SZ, Yang HI, Tzeng YS, Pang CY, Yen PS, et al.
Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 2004;110:1847-54.
England TJ, Sprigg N, Alasheev AM, Belkin AA, Kumar A, Prasad K, et al.
Granulocyte-colony stimulating factor (G-CSF) for stroke: An individual patient data meta-analysis. Sci Rep 2016;6:36567.
Bendall LJ, Bradstock KF. G-CSF: From granulopoietic stimulant to bone marrow stem cell mobilizing agent. Cytokine Growth Factor Rev 2014;25:355-67.
Schäbitz WR, Laage R, Vogt G, Koch W, Kollmar R, Schwab S, et al.
AXIS: A trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke. Stroke 2010;41:2545-51.
Shyu WC, Lin SZ, Lee CC, Liu DD, Li H. Granulocyte colony-stimulating factor for acute ischemic stroke: A randomized controlled trial. CMAJ 2006;174:927-33.
Kadota R, Koda M, Kawabe J, Hashimoto M, Nishio Y, Mannoji C, et al.
Granulocyte colony-stimulating factor (G-CSF) protects oligodendrocyte and promotes hindlimb functional recovery after spinal cord injury in rats. PLoS One 2012;7:e50391.
Nishio Y, Koda M, Kamada T, Someya Y, Kadota R, Mannoji C, et al.
Granulocyte colony-stimulating factor attenuates neuronal death and promotes functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol 2007;66:724-31.
Takahashi H, Yamazaki M, Okawa A, Sakuma T, Kato K, Hashimoto M, et al.
Neuroprotective therapy using granulocyte colony-stimulating factor for acute spinal cord injury: A phase I/IIa clinical trial. Eur Spine J 2012;21:2580-7.
Dela Peña I, Sanberg PR, Acosta S, Tajiri N, Lin SZ, Borlongan CV, et al.
Stem cells and G-CSF for treating neuroinflammation in traumatic brain injury: Aging as a comorbidity factor. J Neurosurg Sci 2014;58:145-9.
Yang DY, Chen YJ, Wang MF, Pan HC, Chen SY, Cheng FC, et al.
Granulocyte colony-stimulating factor enhances cellular proliferation and motor function recovery on rats subjected to traumatic brain injury. Neurol Res 2010;32:1041-9.
England TJ, Abaei M, Auer DP, Lowe J, Jones DR, Sare G, et al.
Granulocyte-colony stimulating factor for mobilizing bone marrow stem cells in subacute stroke: The stem cell trial of recovery enhancement after stroke 2 randomized controlled trial. Stroke 2012;43:405-11.
Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, et al.
Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer's mice. Neuroscience 2009;163:55-72.
Cui L, Wang D, McGillis S, Kyle M, Zhao LR. Repairing the brain by SCF+G-CSF treatment at 6 months postexperimental stroke: Mechanistic determination of the causal link between neurovascular regeneration and motor functional recovery. ASN Neuro 2016;8. pii: 1759091416655010.
Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, et al.
Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation 2006;113:701-10.
Bodine DM, Seidel NE, Gale MS, Nienhuis AW, Orlic D. Efficient retrovirus transduction of mouse pluripotent hematopoietic stem cells mobilized into the peripheral blood by treatment with granulocyte colony-stimulating factor and stem cell factor. Blood 1994;84:1482-91.
Urdziková L, Likavčanová-Mašínová K, Vaněček V, Růžička J, Sedý J, Syková E, et al.
Flt3 ligand synergizes with granulocyte-colony-stimulating factor in bone marrow mobilization to improve functional outcome after spinal cord injury in the rat. Cytotherapy 2011;13:1090-104.
Sanganalmath SK, Abdel-Latif A, Bolli R, Xuan YT, Dawn B. Hematopoietic cytokines for cardiac repair: Mobilization of bone marrow cells and beyond. Basic Res Cardiol 2011;106:709-33.
Zhang XM, Du F, Yang D, Wang R, Yu CJ, Huang XN, et al.
Granulocyte colony-stimulating factor increases the therapeutic efficacy of bone marrow mononuclear cell transplantation in cerebral ischemia in mice. BMC Neurosci 2011;12:61.
Popa-Wagner A, Stöcker K, Balseanu AT, Rogalewski A, Diederich K, Minnerup J, et al.
Effects of granulocyte-colony stimulating factor after stroke in aged rats. Stroke 2010;41:1027-31.
Luo J, Zhang HT, Jiang XD, Xue S, Ke YQ. Combination of bone marrow stromal cell transplantation with mobilization by granulocyte-colony stimulating factor promotes functional recovery after spinal cord transection. Acta Neurochir (Wien) 2009;151:1483-92.
Guo X, Bu X, Jiang J, Cheng P, Yan Z. Enhanced neuroprotective effects of co-administration of G-CSF with simvastatin on intracerebral hemorrhage in rats. Turk Neurosurg 2012;22:732-9.
Shin YK, Cho SR. Exploring erythropoietin and G-CSF combination therapy in chronic stroke patients. Int J Mol Sci 2016;17:463.
Fesli A, Sari A, Yilmaz N, Comelekoglu U, Tasdelen B. Enhancement of nerve healing with the combined use of amniotic membrane and granulocyte-colony-stimulating factor. J Plast Reconstr Aesthet Surg 2014;67:837-43.
Acosta SA, Tajiri N, Shinozuka K, Ishikawa H, Sanberg PR, Sanchez-Ramos J, et al.
Combination therapy of human umbilical cord blood cells and granulocyte colony stimulating factor reduces histopathological and motor impairments in an experimental model of chronic traumatic brain injury. PLoS One 2014;9:e90953.
Willing AE, Vendrame M, Mallery J, Cassady CJ, Davis CD, Sanchez-Ramos J, et al.
Mobilized peripheral blood cells administered intravenously produce functional recovery in stroke. Cell Transplant 2003;12:449-54.
Iskander A, Knight RA, Zhang ZG, Ewing JR, Shankar A, Varma NR, et al.
Intravenous administration of human umbilical cord blood-derived AC133+ endothelial progenitor cells in rat stroke model reduces infarct volume: Magnetic resonance imaging and histological findings. Stem Cells Transl Med 2013;2:703-14.
Shahaduzzaman M, Golden JE, Green S, Gronda AE, Adrien E, Ahmed A, et al.
A single administration of human umbilical cord blood T cells produces long-lasting effects in the aging hippocampus. Age (Dordr) 2013;35:2071-87.
Zhao LR, Piao CS, Murikinati SR, Gonzalez-Toledo ME. The role of stem cell factor and granulocyte-colony stimulating factor in treatment of stroke. Recent Pat CNS Drug Discov 2013;8:2-12.
Toth ZE, Leker RR, Shahar T, Pastorino S, Szalayova I, Asemenew B, et al.
The combination of granulocyte colony-stimulating factor and stem cell factor significantly increases the number of bone marrow-derived endothelial cells in brains of mice following cerebral ischemia. Blood 2008;111:5544-52.
Tsuji T, Nishimura-Morita Y, Watanabe Y, Hirano D, Nakanishi S, Mori KJ, et al.
A murine stromal cell line promotes the expansion of CD34high+-primitive progenitor cells isolated from human umbilical cord blood in combination with human cytokines. Growth Factors 1999;16:225-40.
Piao CS, Li B, Zhang LJ, Zhao LR. Stem cell factor and granulocyte colony-stimulating factor promote neuronal lineage commitment of neural stem cells. Differentiation 2012;83:17-25.
Borlongan CV. Bone marrow stem cell mobilization in stroke: A 'bonehead' may be good after all! Leukemia 2011;25:1674-86.
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