Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo

Al-Khaldi, Abdulaziz; Eliopoulos, Nicoletta; Martineau, Daniel; Lejeune, Laurence; Lachapelle, Kevin; Galipeau, Jacques

doi:10.1038/sj.gt.3301934

Cited by 195 publications

(139 citation statements)

References 28 publications

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“…Considering that hMSCs are strong inducers of angiogenesis [38], the infiltration of scaffolds by host (mouse) cells such as vascular cells would supply oxygen and nutrients to the implanted hMSCs. Indeed, implanted hMSCs have been reported to cause angiogenesis via host-derived vascular cells rather than via transdifferentiation of the hMSCs into endothelial cells [38,39]. We could not detect mineralized tissue within the osteogenic scaffolds that lacked hMSCs, and, therefore, it is likely that the bone tissue that was formed within the implants originated from the hMSCs.…”

Section: Discussionmentioning

confidence: 99%

In vivo bone formation by human marrow stromal cells in biodegradable scaffolds that release dexamethasone and ascorbate-2-phosphate

Kim

Suh

et al. 2005

Biochemical and Biophysical Research Communications

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Section: Discussionmentioning

confidence: 99%

In vivo bone formation by human marrow stromal cells in biodegradable scaffolds that release dexamethasone and ascorbate-2-phosphate

Kim

Suh

et al. 2005

Biochemical and Biophysical Research Communications

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“…Moreover, multiple sublineages of bone marrow cells include Lin-c-kit+, CD34+ and CD34-sublineages (19,20). Besides effectively stimulating angiogenesis, CD 34+ and CD34-bone marrow-derived MSCs also release VEGF to play an integral role in the angiogenic effect (21). The hematopoietic CD34-'side population' has the potential to differentiate into endothelial cells and cardiomyocytes, and there is histological evidence for increased neovascularization and cardiomyocytes (22).…”

Section: Discussionmentioning

confidence: 99%

A promising strategy for the treatment of ischemic heart disease: Mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats

Gao

Wang

et al. 2007

Canadian Journal of Cardiology

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F Gao, T He, HB Wang, et al. A promising strategy for the treatment of ischemic heart disease: Mesenchymal stem cellmediated vascular endothelial growth factor gene transfer in rats. Can J Cardiol 2007;23(11):891-898.BACKGROUND: Treatment of ischemic heart disease (IHD) remains a worldwide problem. Gene therapy, and recently, cell transplantation, have made desirable progress. A combination of appropriate stem cells and angiogenic genes appears promising in treating IHD. OBJECTIVE: To study the results of angiogenesis and myogenesis induced by transplantation of the adenovirus carrying human vascular endothelial growth factor 165 (Ad-hVEGF 165 )-transfected mesenchymal stem cells (MSCs) in IHD compared with direct MSC transplantation or Ad-hVEGF 165 delivery. METHODS: Cultured MSCs were transfected by Ad-hVEGF 165 , and secreted VEGF was measured by ELISA in vitro. Ad-hVEGF 165 -transfected MSCs (MSC/VEGF group), MSCs (MSC group), AdhVEGF 165 (VEGF group) or a serum-free medium (control group) was injected into syngeneic Wistar rats immediately after left coronary artery occlusion. All cells were marked with CM-DiI (Molecular Probes, USA) before transplantation. One week after treatment, messenger RNA expression of hVEGF 165 in the MSC/VEGF group was found to be significantly higher than in other groups by reverse transcriptase-polymerase chain reaction analysis. One month after cell transplantation, left ventricular (LV) ejection fraction, capillary density of the infarcted region, infarct size and hemodynamic parameters (including LV end-diastolic pressure, LV+dP/dt and LV-dP/dt) were measured and immunohistochemical analysis was performed. RESULTS: A high level of VEGF was expressed by Ad-hVEGF 165 -transfected MSCs. LV ejection fraction, mean capillary density of the infarcted region and hemodynamic parameters were significantly improved in the MSC/VEGF group compared with the MSC group, the VEGF group and the control group (P<0.001 for all). Partly transplanted MSCs showed the cardiomyocyte phenotype, expressed desmin and cardiac troponin T, and resulted in angiogenesis in the ischemic myocardium. However, a few transplanted MSCs incorporated into the vascular structure and most of the new vascular components were host-derived. CONCLUSIONS: The combined strategy of MSC transplantation and VEGF gene therapy can produce effective myogenesis and hostderived angiogenesis, resulting in the prevention of progressive heart dysfunction after myocardial infarction.

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“…In fact, MSC transplantation has been performed in the field of ischemic diseases, and it has been suggested that its plausible effects would be mediated largely through paracrine actions of locally released arteriogenic cytokines, including bFGF and VEGF (11,13,30). Although bFGF or VEGF has the independent ability to induce angiogenesis, the use of bFGF and VEGF in a coordinated manner has been shown to induce functional neovascularization (31).…”

Section: Discussionmentioning

confidence: 99%

Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

et al. 2008

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OBJECTIVE-Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats.RESEARCH DESIGN AND METHODS-MSCs were isolated from bone marrow of adult rats and transplanted into hind limb skeletal muscles of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF), capillary number-to-muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated.RESULTS-VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF, and decreased capillary number-to-muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in STZ-induced diabetic rats, which was normalized by MSC transplantation. D iabetic polyneuropathy (DPN) is the most common complication of diabetes. It is estimated that ϳ20 -30% of diabetic patients are affected by symptomatic DPN (1). Generally, DPN develops symmetrically in a length-dependent fashion, with dying back or dropout of the longest nerve fibers; both myelinated and unmyelinated, large and small are affected. Diabetic patients suffer from various symptoms of DPN, such as spontaneous pain, hyperalgesia, and diminished sensation (2). It has been shown that tight glycemic control is effective in slowing the progression of DPN but cannot completely prevent it (3). Therefore, additional therapeutic strategies are required. CONCLUSIONS-TheseNeural cell degeneration and decreased nerve blood flow (NBF) have been recognized as pathophysiologically characteristic features of DPN (4). Therefore, therapeutic agents that could act as both neurotrophic and angiogenic factors would be useful for the treatment of DPN even at an advanced stage. We previously demonstrated that local administration of basic fibroblast growth factor (bFGF) by intramusclar injection with crosslinked gelatin hydrogel improved the impaired nerve functions of streptozotocin (STZ)-induced diabetic rats, including amelioration of decreased NBF, hypoalgesia, and the delayed motor nerve conduction velocity (MNCV) on the treated side of sciatictibial nerves and that these effects were maintained for at least 30 days (5). Schratzberger et al. (6) showed that vascular endothelial growth factor (VEGF) gene transfer significantly increased the NCV and NBF as well as the vascular densities in muscle and peripheral nerv...

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Postnatal bone marrow stromal cells elicit a potent VEGF-dependent neoangiogenic response in vivo

Cited by 195 publications

References 28 publications

In vivo bone formation by human marrow stromal cells in biodegradable scaffolds that release dexamethasone and ascorbate-2-phosphate

In vivo bone formation by human marrow stromal cells in biodegradable scaffolds that release dexamethasone and ascorbate-2-phosphate

A promising strategy for the treatment of ischemic heart disease: Mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats

Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats

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