Administration Of CD34 Research Articles

Impact of CD34 positive cell dose in donor graft on the outcomes after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide – A retrospective single-center study with a Japanese cohort

BackgroundHaploidentical peripheral blood stem cell transplantation (haplo-PBSCT) with post-transplant cyclophosphamide (PTCy) is an important therapeutic option for patients lacking an HLA-matched donor. However, the significance of CD34+ cell dose in grafts has not been fully elucidated. ObjectiveWe aimed to explore the impact of CD34+ cell dose on outcomes after haplo-PBSCT with PTCy. Study DesignWe retrospectively investigated 111 consecutive patients who underwent haplo-PBSCT with PTCy or HLA-matched PBSCT from related donors. ResultsThere were no statistically significant differences in 3-year overall survival (p = 0.559) or progression-free survival (p = 0.974) between haplo-PBSCT and matched PBSCT. Delayed neutrophil engraftment and a lower incidence of graft-versus-host disease were observed in haplo-PBSCT. The median dose of CD34+ cells was 4.9 × 106 /kg in 57 haplo-PBSCT and 4.5 × 106 /kg in 54 matched PBSCTs. Importantly, patients who underwent haplo-PBSCT with the administration of CD34+ cell at a dose of ≥4.0 × 106 /kg significantly had improved OS (p = 0.015) and decreased incidence of disease relapse (p = 0.001) without increasing incidence of GVHD. ConclusionOur data suggest that a higher dose of CD34+ cells in haplo-PBSCT with PTCy positively impacts the outcomes without an increase of GVHD.

CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial

BackgroundTreatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10–15% of the patients in this context will be candidate for curative resection arising other 10–13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection.Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. Methods/Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. Secondary aims areto compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. Study designProspective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DiscussionThe number of CD133 + obtained from peripheral blood after G –CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. Trial registrationClinicalTrials.gov, ID NCT03803241.

Intramyocardial autologous CD34+ cell therapy for refractory angina: A meta-analysis of randomized controlled trials.

Previous studies have demonstrated that intramyocardial human CD34+ cells may relieve symptoms and improve clinical outcomes in chronic refractory angina unresponsive to optimal medical therapy or not amenable to revascularization. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the impact of human CD34+ cells compared with placebo in chronic refractory angina. Primary efficacy outcomes in our analysis were angina frequency and exercise time. Primary safety outcomes included major adverse cardiovascular events such as myocardial infarction (MI), stroke and death. Three eligible randomized trials including 269 patients (placebo = 90, CD34+ = 179) were included. Dose of auto-CD34+ cells ranged from 5 × 104 to 5 × 105 cells/kg. Follow-up ranged from 6 to 24 months. In a pooled analysis, administration of CD34+ cells decreased the risk of all-cause mortality [OR 0.24, 95% CI (0.08-0.73), p = 0.01], reduced angina frequency [mean difference -2.91, 95% CI (-4.57 to -1.25), p = 0.0006] and improved exercise time [mean difference 58.62 s, 95% CI (21.19 to 96.06), p = 0.02] compared with control group. However, there was no significant difference in the risk of myocardial infarction (MI) and stroke between groups. In a meta-analysis, intra-myocardial CD34+ cell therapy was superior to placebo in improving risk of all - cause mortality, angina frequency with an increase in exercise time, without a significant increase in adverse events. This analysis supports further trials of CD34+ cell therapy for ischemic heart disease.

CD34+ selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation.

Poor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34+ selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n=25) or mismatched related (n=25) donors. Within 8weeks, a significant increase in median neutrophil counts (0·6 vs. 1·516×109 /l, P<0·05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs. 0, P<0·0001 and <0·001), were observed, and 78·8% of patients resolved one or two of their cytopenias. 36·5% had a complete haematological response. Median lymphocyte counts for CD3+ , CD3+ CD4+ , CD19+ and CD56+ increased 8·3-, 14·2-, 22.- and 1·6-fold. The rate of de novo acute graft-versus-host disease (GvHD) grade I-III was only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred. Patients who responded to SCB displayed a trend toward better overall survival (OS) (P=0·07). Thus, administration of CD34+ selected SCBs from alternative donors is safe and effective. Further studies are warranted to clarify the impact on immune reconstitution and survival.

Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury.

Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis.

Ex vivo expansion of circulating CD34+ cells enhances the regenerative effect on rat liver cirrhosis

Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34+ cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34+ cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34+ cells were injected via the spleen. After 7 days, CD34+ cells were effectively expanded in a serum-free culture medium. Expanded CD34+ cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34+ cells increased compared with nonexpanded CD34+ cells. Expanded CD34+ cell transplantation reduced liver fibrosis, with a decrease of αSMA+ cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34+ cells over non-expanded CD34+ cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34+ cells and aggravated liver fibrosis. These findings suggest that expanded CD34+ cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model.

Human peripheral blood CD34+ cells attenuate oleic acid–induced acute lung injury in rats

Background aimsAdult stem cell–based therapy is a promising novel approach for treatment of acute lung injury (ALI). In this study, we evaluated the therapeutic effect of isolated human peripheral blood CD34+ progenitor cells in an ALI rat model, induced by oleic acid (OA) injection. MethodsSeventy-five adult female rats were used in this study. Group A, control without treatment, and group B, control injected with phosphate-buffered saline, comprised 15 rats each; the remaining 45 rats were injected with OA to induce ALI and were further subdivided into 3 groups: group C (ALI group, 15 rats), group D (ALI and fibroblast group, 15 rats) and group E (ALI and CD34+ cell group, 15 rats). ResultsCD34+ cells transplantation in rats with OA-induced lung injury improves the arterial PaO2 and wet/dry ratio, reduces infiltration of inflammatory cells and decreases lung vascular permeability as determined by reduced intra-alveolar and interstitial patchy congestion and hemorrhage as well as decreased interstitial edema. Additionally, lung inflammation determined by expression of the pro-inflammatory mediators intercellular adhesion molecule 1 and tumor necrosis factor-α was attenuated in CD34+ cell–treated rats at 6, 24 and 48 h post-OA challenge compared with non-treated rats. Moreover, the expression of anti-inflammatory molecule interleukin-10 was up-regulated in the lung of OA-induced ALI rats after administration of CD34+ cells. The important finding was that human TNF-α-induced protein 6 (TSG-6) gene expression was significantly up-regulated in rats treated with CD34+ cells. ConclusionsThe freshly isolated human peripheral blood–derived CD34+ cells may be used as an important source of stem cells that improve ALI. The anti-inflammatory properties of CD34+ cells in the lung are explained, at least in part, by activation of CD34+ cells to express TSG-6.

Biochemical and Parasitological Studies on the Effect of hUCB-Selected CD34(+) Progenitor/Stem Cells in Mice Infected with Schistosoma mansoni.

Background and Objectives:Placenta and blood that remained in the umbilical cord is routinely available as a discarded tissue after deliveries and it is free of any legal, moral, ethical or religious objections, providing a high number of multipotent CD34+ progenitor and stem cells. Using ex vivo isolated CD34+ cells from human umbilical cord blood (hUCB) have emerged as promising candidates to treat various diseases, including exogenous pathogenic infections. We have expanded to build a rational approach to study the effect of CD34+ cells after damaged liver tissues by the devastating human parasitic flatworm Schistosoma mansoni.Methods and Results:Experimental studies were conducted in the Department of Zoology, Faculty of Science and Departments of Parasitology and Physiology, Faculty of Medicine, SCU, Egypt. We have studied the impact of ex vivo preparation of CD34+ cells from hUCB on S. mansoni-induced liver fibrosis de novo, and treated for shorter and longer periods in vivo. Ova count, ALT and albumin were measured at specific time interval and histopathological examination of liver was conducted to confirm the biochemical results. The data obtained were statistically analyzed by ANOVA between groups. It was found that the administration of CD34+ cells have modestly reduced liver damage; reduced the S. mansoni infection associated elevation in serum levels of ALT; significantly improved serum levels of albumin and reduced egg granuloma diameter in the livers.Conclusions:We demonstrated that CD34+ cells can markedly ameliorated liver fibrosis in vivo and may be beneficial for therapy to recover organ structure and/or function of S. mansoni-infected mice.

Ex-vivo expanded human blood-derived CD133+ cells promote repair of injured spinal cord

Human blood-derived CD133+ cell populations, which are believed to represent a hematopoietic/endothelial progenitor fraction, have the ability to promote the repair of injured spinal cord in animal models. However, the mechanisms by which CD133+ cell transplantation promotes spinal cord regeneration remain to be clarified. Another possible hurdle on the way to clinical applicability of these cells is their scarce representation in the overall population of mononuclear cells. We therefore analyzed and compared ex-vivo expanded human cord blood derived CD133+ cells with freshly isolated CD133+ cells as well as corresponding CD133− control mononuclear cells in respect to their ability to promote spinal cord repair using in vitro assays and cell transplantation into a mouse spinal cord injury model. In vitro, expanded cells as well as fresh CD133+ cells formed endothelial progenitor cell (EPC) colonies, whereas CD133− cells formed no EPC colonies. In vivo, the administration of fresh CD133+ and expanded cells enhanced angiogenesis, astrogliosis, axon growth and functional recovery after injury. In contrast, the administration of CD133− cells failed to promote axon growth and functional recovery, but moderately enhanced angiogenesis and astrogliosis. In addition, high-dose administration of expanded cells was highly effective in the induction of regenerative processes at the injured spinal cord.

Abstract 6: Therapeutic Angiogenesis by Human CD34+ Hematopoietic Stem Cells via Exosomes-Mediated MicroRNA Transfer

Introduction: Locally transplanted human CD34+ hematopoietic stem cells have stimulated neovascularization in preclinical studies and have been associated with functional improvements in phase I and II clinical trials of patients with ischemic cardiovascular diseases. Recently, we have demonstrated that membrane-bound nano-vesicles called exosomes are one of the primary pro-angiogenic components of human CD34+ cell paracrine secretion that induced angiogenesis independently of the cells. Here, we hypothesize that the functional benefits associated with CD34+ cell therapy are primarily mediated by the secretion of exosomes (Exo), and that CD34+ Exo transfer pro-angiogenic microRNAs to promote angiogenesis and ischemic tissue repair. Methods and Results: Therapeutic potential of CD34+ Exo isolated from adult human peripheral blood-derived CD34+ cells was evaluated in a mouse model of hind limb ischemia (HLI). Similar to CD34+ cells, administration of CD34+ Exo from equal number of cells induced angiogenesis and tissue repair; it significantly improved perfusion (ratio: 1.01±0.04 v 0.57±0.1, P&lt;0.05), increased capillary density (1.8±0.3/HPF v 0.9±0.1/HPF, p&lt;0.001) and prevented ischemic leg amputation (16% v 100%), compared to Exo from non-angiogenic, CD34+ cell-depleted-mononuclear cells (MNC Exo). Our microarray data and confirmatory tests revealed that unlike MNC Exo, CD34+ Exo are enriched in pro-angiogenic miRNAs such as miR-126. Flow cytometry and live confocal imaging demonstrated that Cy3-tagged miRNA in CD34+ Exo is directly transferred to endothelial cells in vitro and in ischemic tissues in vivo; concurrent loss of function gain of function studies prove that direct transfer of miR-126 is crucial for CD34+ Exo-induced angiogenesis and functional recovery. To address whether exosome secretion is needed for miR-126 transfer, we are exploring the effect of inhibition of exosome secretion from CD34+ cells. Conclusion: CD34+ exosomes transfer the pro-angiogenic miR-126 to endothelial cells in the ischemic tissues to induce angiogenesis and ischemic tissue repair. Our study illustrates a mechanism of stem cell communication involving intercellular traffic of miRNAs via exosomes to induce functional recovery.

Human cord blood CD133+ cells exacerbate ischemic acute kidney injury in mice

Acute kidney injury (AKI) in humans has few therapeutic options. In experimental models, administration of progenitor cells facilitates recovery from AKI. Human umbilical cord-derived CD133(+) progenitor cells promote endothelial repair in ischemic limb, heart and brain tissue. We examined the effects of human CD133(+) progenitor cells in bilateral ischemia-reperfusion (I/R) kidney injury in non-obese diabetic severe combined immunodeficient mice. CD133(+) cells from human cord blood were injected intravenously at the time of reperfusion and the extent of injury was determined by plasma biochemistry and kidney histology. In mice with I/R, fluorescently labeled CD133(+) cells were detected in blood 2 min after injection but decreased rapidly thereafter with no evidence of homing to the kidneys. In mice subjected to I/R, CD133(+) cells significantly increased plasma urea and Cr at 24 h compared to vehicle- or CD133(-) cell-treated mice. CD133(+) cells exacerbated tubular necrosis and apoptosis, increased plasma tumor necrosis factor-α and increased kidney neutrophil infiltration. In contrast, CD133(+) cells did not affect tubular cell proliferation. Administration of CD133(+) cells to FVB/N mice post-I/R also augmented kidney injury. These data indicate that human cord blood-derived CD133(+) cells unexpectedly exacerbate ischemic AKI in mice, possibly through soluble factors. Our study highlights the importance of caution in cell-based therapies for human AKI.

Cardiac stem cell therapy

In cardiac stem cell therapy, the past decade has been interesting with respect to preclinical and clinical research. The high diversity of applied stem cell populations and evaluation methods represent a challenge to fully understand the impact of stem cell administration, leaving uncertain answers to the questions that have been dealt with thus far. In the present work, registered studies in cardiac stem cell therapy are summarized and the study aims are highlighted. Furthermore, preliminary data on the additional intramyocardial administration of CD133+ stem cells in patients undergoing mitral valve surgery are presented.

Administration of Human Peripheral Blood-Derived CD133+ Cells Accelerates Functional Recovery in a Rat Spinal Cord Injury Model

Magnetically isolated, peripheral blood-derived CD133+ cells were used as the therapeutic agent of spinal cord injury (SCI). A rat model was used to investigate the hypothesis that the cell therapy using this clinically accessible cell fraction could be an attractive option for injured spinal cord. Given the capacity for the peripheral blood-derived CD133+ cells in vivo to produce neurogenesis via vasculogenesis as the feasible candidate for SCI in the clinical setting, the focus of the experiment was to investigate whether the cells could contribute to histologic and functional recovery of SCI after transplantation. No evidence for peripheral blood-derived CD133+ cells application to SCI and no experimental studies showed functional recovery from SCI using this cell fraction have been published. Contusion SCI was induced by placing a 25-g rod onto the spinal cord for 90 seconds in athymic nude rats. CD133+ cells or phosphate-buffered saline was administered intravenously immediately after SCI. The animals were analyzed at specific times after transplantation by several methods to examine histologic vasculogenesis and neurogenesis and to confirm functional recovery from SCI. After cell transplantation, intrinsic angiogenesis and axonal regeneration were enhanced, and cavity formation was reduced in injured spinal cord, histologically, with significant functional recovery. Gene expression of vascular endothelial growth factor increased in the cell-administrated group. The administration of CD133+ cells has a therapeutic potential to a rat spinal cord injury model and could be an optional treatment for spinal cord injury in the clinical settings.

Antitumor Activity of Human CD34+ Cells Expressing Membrane-Bound Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (mTRAIL).

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is expected to play a key role in anti-cancer therapy due to its high cancer cell-specificity and potent antitumor activity. The clinical development of soluble (s)TRAIL is however hampered by several limitations, includingshort plasma half-life;liver toxicity;tumor cell resistance.To overcome these limitations, we used CD34+ cells transduced with an adenovirus encoding the full-length human TRAIL gene (CD34−TRAIL+) as vehicles for intra-tumor delivery of membrane-bound (m)TRAIL. The mean (±SD) transduction efficiency of CD34+ cells exposed to a multiplicity of infection (MOI) of 500 was 83 ± 8% (range 70 – 95%) with a cell viability ≥85%. In vitro, exposure of the sTRAIL-sensitive KMS-11 cell line to CD34−TRAIL+, but not mock-transduced CD34+ cells consistently resulted in caspase-3, -8, and -9 activation and in PARP cleavage, as well as in potent induction of apoptosis (up to 80% after a 48-hour co-culture). Exposure of the sTRAIL-resistant JVM-2 cell line to CD34−TRAIL+ cells resulted in significant levels of tumor cell death (up to 50% after a 48-hour co-culture). Studies in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice xenografted with KMS-11 cell line showed that CD34−TRAIL+ cells significantly increased the median survival of mice bearing early-stage (92 vs 55 days, P ≤ 0.0001) and advanced-stage (83 vs 55 days, P ≤ 0.0001) disease, as compared with controls. Additionally, CD34−TRAIL+ cells significantly prolonged the median survival of mice xenografted with the sTRAIL-resistant JVM-2 (40 vs 31 days, P ≤ 0.0001) and SU-DHL-4V (38 vs 30 days, P ≤ 0.0001) cell lines. No obvious toxicity was observed upon administration of CD34−TRAIL+ cells. Histological analysis of subcutaneous lymphoma revealed an efficient tumor homing of transduced cells and high level expression of the agonistic TRAIL-R2 receptor by tumor endothelial cells. Following injection of CD34−TRAIL+ cells, but not mock-transduced CD34+ cells, TUNEL staining revealed increasing amounts of apoptotic cells with a 21-fold increase of the apoptotic index at 120 hour post-injection. Additionally, CD34−TRAIL+ cells induced signs of vascular damage leading to a progressive disintegration of the vascular bed, suggesting that tumor endothelial cells represent an early target of CD34−TRAIL+ cells. Our experiments show that:in vitro, the co-culture of tumor cells and CD34−TRAIL+ cells resulted in a marked apoptosis of both sTRAIL-sensitive and sTRAIL-resistant tumor cells;in vivo, injection of CD34−TRAIL+ cells in mice bearing advanced-stage tumors as well as sTRAIL-resistant tumors was associated with a significant prolongation of survival.These results show that CD34−TRAIL+ cells might be an efficient vehicle for mTRAIL delivery to tumors, where they exert a potent antitumor effect possibly mediated by both direct tumor cell killing and indirect vascular-disrupting mechanisms.

CD34 + Cells Home, Proliferate, and Participate in Capillary Formation, and in Combination With CD34 − Cells Enhance Tube Formation in a 3-Dimensional Matrix

Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies. Effects of the hematopoietic stem cell-containing CD34+ cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34+ cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34+ cells in and around capillary sprouts. CD34+ cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene-transduced CD34+ cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34+ cells alone stimulated neovascularization by 17%. Coculture with CD34- cells led to 68% enhancement of neovascularization, whereas CD34- cells displayed a variable response by themselves. Cell-cell contact between CD34+ and CD34- cells facilitated endothelial differentiation of CD34+ cells. Our data suggest that administration of CD34+-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34- cells.

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34(+) cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34(+) cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model