Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

Sun, Lixin; Lee, Jeongwu; Fine, Howard A.

doi:10.1172/jci200420001

Cited by 204 publications

(52 citation statements)

References 62 publications

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“…Upregulation of CXCL12/stromal-derived factor 1(SDF-1) has been reported in the ischemic penumbra [87,88], and its interaction with (CXCR-4)/CD184 (expressed by all three cell populations used in our study) is known to promote migration of cbMNCs [89]. Also, enhanced expression of SCF has been reported in neurons within the injured hemisphere [90] and might have played a role in directed migration of transplanted cb/cmMSCs, both of which had significant expression of the SCF receptor CD117, as shown in our comparative flow-cytometry experiment.…”

Section: Discussionmentioning

confidence: 77%

Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model

et al. 2014

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IntroductionStroke is the second leading cause of death worldwide, claims six lives every 60 seconds, and is a leading cause of adult disability across the globe. Tissue plasminogen activator, the only United States Food and Drug Administration (FDA)-approved drug currently available, has a narrow therapeutic time window of less than 5 hours. In the past decade, cells derived from the human umbilical cord (HUC) have emerged as a potential therapeutic alternative for stroke; however, the most effective HUC-derived cell population remains unknown.MethodsWe compared three cell populations derived from the human umbilical cord: cord blood mononuclear cells (cbMNCs); cord blood mesenchymal stromal cells (cbMSCs), a subpopulation of cbMNCs; and cord matrix MSCs (cmMSCs). We characterized these cells in vitro with flow cytometry and assessed the cells’ in vivo efficacy in a 2-hour transient middle cerebral artery occlusion (MCAo) rat model of stroke. cbMNCs, cbMSCs, and cmMSCs were each transplanted intraarterially at 24 hours after stroke.ResultsA reduction in neurologic deficit and infarct area was observed in all three cell groups; however, this reduction was significantly enhanced in the cbMNC group compared with the cmMSC group. At 2 weeks after stroke, human nuclei-positive cells were present in the ischemic hemispheres of immunocompetent stroke rats in all three cell groups. Significantly decreased expression of rat brain-derived neurotrophic factor mRNA was observed in the ischemic hemispheres of all three cell-treated and phosphate-buffered saline (PBS) group animals compared with sham animals, although the decrease was least in cbMNC-treated animals. Significantly decreased expression of rat interleukin (IL)-2 mRNA and IL-6 mRNA was seen only in the cbMSC group. Notably, more severe complications (death, eye inflammation) were observed in the cmMSC group compared with the cbMNC and cbMSC groups.ConclusionsAll three tested cell types promoted recovery after stroke, but cbMNCs showed enhanced recovery and fewer complications compared with cmMSCs.

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Section: Discussionmentioning

confidence: 77%

Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model

et al. 2014

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“…Moreover, SCF has been identified as a potent chemoattractant for the neural progenitors and as a factor triggering outgrowth-promoting mechanisms [67–69]. It was found previously that SCF is activated in the selected models of injury and exerts protective activity in both non-neural and neural tissue [70–72].…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotective Effect Exerted by Oligodendroglial Progenitors on Ischemically Impaired Hippocampal Cells

Sypecka

Sarnowska

2013

Mol Neurobiol

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Oligodendrocyte progenitor cells (OPCs) are the focus of intense research for the purpose of cell replacement therapies in acquired or inherited neurodegenerative disorders, accompanied by ongoing hypo/demyelination. Recently, it has been postulated that these glia-committed cells exhibit certain properties of neural stem cells. Advances in stem cell biology have shown that their therapeutic effect could be attributed to their ability to secret numerous active compounds which modify the local microenvironment making it more susceptible to restorative processes. To verify this hypothesis, we set up an ex vivo co-culture system of OPCs isolated from neonatal rat brain with organotypic hippocampal slices (OHC) injured by oxygen-glucose deprivation (OGD). The presence of OPCs in such co-cultures resulted in a significant neuroprotective effect manifesting itself as a decrease in cell death rate and as an extension of newly formed cells in ischemically impaired hippocampal slices. A microarray analysis of broad spectrum of trophic factors and cytokines expressed by OPCs was performed for the purpose of finding the factor(s) contributing to the observed effect. Three of them—BDNF, IL-10 and SCF—were selected for the subsequent functional assays. Our data revealed that BDNF released by OPCs is the potent factor that stimulates cell proliferation and survival in OHC subjected to OGD injury. At the same time, it was observed that IL-10 attenuates inflammatory processes by promoting the formation of the cells associated with the immunological response. Those neuroprotective qualities of oligodendroglia-biased progenitors significantly contribute to anticipating a successful cell replacement therapy.

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“…The migratory tropism toward tumors has been observed when MSCs are administered by intravenous [14], intraarterial [15], or peritumoral routes [16]. The mechanism of migration is poorly understood, but has been shown to be dependent upon the cytokine/receptor pairs SDF-1/CXCR4 [15,17,18], SCF-c-Kit [19,20], HGF/c-Met [21], VEGF/VEGFR [22], PDGF/PDGFr [15], MCP-1/CCR2 [23], and HMGB1/RAGE [24,25], as well as cellular adhesion molecules [18,26,27]. Migration to tumors, however, is non-specific as exogenously administered MSCs have also been shown to localize to the lung [14,28–32], bone marrow [29,30,33,34], and lymphoid organs [35,36]; and prior whole body irradiation tends to expand the distribution of MSCs in the body to multiple organs [28,30].…”

Section: Mesenchymal Stem Cells Migrate To Tumorsmentioning

confidence: 99%

The Oncogenic Potential of Mesenchymal Stem Cells in the Treatment of Cancer: Directions for Future Research

Momin¹,

Vela²,

Zaidi³

et al. 2010

CIR

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Mesenchymal stem cells (MSCs) represent a promising new approach to the treatment of several diseases that are associated with dismal outcomes. These include myocardial damage, graft versus host disease, and possibly cancer. Although the potential therapeutic aspects of MSCs continue to be well-researched, the possible hazards of MSCs, and in particular their oncogenic capacity are poorly understood. This review addresses the oncogenic and tumor-supporting potential of MSCs within the context of cancer treatment. The risk for malignant transformation is discussed for each stage of the clinical lifecycle of MSCs. This includes malignant transformation in vitro during production phases, during insertion of potentially therapeutic transgenes, and finally in vivo via interactions with tumor stroma. The immunosuppressive qualities of MSCs, which may facilitate evasion of the immune system by a tumor, are also addressed. Limitations of the methods employed in clinical trials to date are reviewed, including the absence of long term follow-up and lack of adequate screening methods to detect formation of new tumors. Through discussions of the possible oncogenic and tumor-supporting mechanisms of MSCs, directions for future research are identified which may eventually facilitate the future clinical translation of MSCs for the treatment of cancer and other diseases.

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Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

Cited by 204 publications

References 62 publications

Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model

Intraarterial transplantation of human umbilical cord blood mononuclear cells is more efficacious and safer compared with umbilical cord mesenchymal stromal cells in a rodent stroke model

The Neuroprotective Effect Exerted by Oligodendroglial Progenitors on Ischemically Impaired Hippocampal Cells

The Oncogenic Potential of Mesenchymal Stem Cells in the Treatment of Cancer: Directions for Future Research

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