Angiogenic Potential of Bone Marrow Derived CD133+ and CD271+ Intramyocardial Stem Cell Trans- Plantation Post MI

Sasse, Sarah K.; Skorska, Anna; Lux, Cornelia A.; Steinhoff, Gustav; Dávid, Róbert; Gaebel, Ralf

doi:10.3390/cells9010078

Cited by 23 publications

(19 citation statements)

References 47 publications

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“…We detected CD271 + subpopulations in adult MSC [24,26]. Similar to us, others have reported that all fibroblast colony-forming cells (CFU-F) in human BM are present and rare [38,39].…”

Section: Discussionsupporting

confidence: 89%

“…Similar to us, others have reported that all fibroblast colony-forming cells (CFU-F) in human BM are present and rare [38,39]. While the total number of the MACS-purified CD271 + from sternal BM accounted approx.~5500 per mL of the aspirate [26] in our study, the iliac crest BM aspirate accounted in 2-2.5 fold more MSC progenitors ranging from 1000-15,000 per mL of aspirate [38,40]. Hence, those studies have evidenced a linear relationship between numbers of mononuclear cells and mesenchymal progenitor cells as well as positive correlation between these mesenchymal progenitors and CFU-F counts.…”

Section: Discussionsupporting

confidence: 78%

“…CD133 + and CD271 + cells were enriched by positive magnetic selection using the magnet activated cell sorting (MACS) system (Miltenyi Biotec, Bergisch Gladbach, Germany), using direct labeling in case of CD133 + and an indirect labeling (CD271-APC/anti-APC-micro beads; Miltenyi Biotec) for CD271 + cells. Purity and viability of all cell isolations were verified by flow cytometry as previously described [24][25][26].…”

Section: Cell Isolationmentioning

confidence: 99%

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Dose-Independent Therapeutic Benefit of Bone Marrow Stem Cell Transplantation after MI in Mice

et al. 2020

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Several cell populations derived from bone marrow (BM) have been shown to possess cardiac regenerative potential. Among these are freshly isolated CD133+ hematopoietic as well as culture-expanded mesenchymal stem cells. Alternatively, by purifying CD271+ cells from BM, mesenchymal progenitors can be enriched without an ex vivo cultivation. With regard to the limited available number of freshly isolated BM-derived stem cells, the effect of the dosage on the therapeutic efficiency is of particular interest. Therefore, in the present pre-clinical study, we investigated human BM-derived CD133+ and CD271+ stem cells for their cardiac regenerative potential three weeks post-myocardial infarction (MI) in a dose-dependent manner. The improvement of the hemodynamic function as well as cardiac remodeling showed no therapeutic difference after the transplantation of both 100,000 and 500,000 stem cells. Therefore, beneficial stem cell transplantation post-MI is widely independent of the cell dose and detrimental stem cell amplification in vitro can likely be avoided.

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“…We detected CD271 + subpopulations in adult MSC [24,26]. Similar to us, others have reported that all fibroblast colony-forming cells (CFU-F) in human BM are present and rare [38,39].…”

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 78%

Section: Cell Isolationmentioning

confidence: 99%

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Dose-Independent Therapeutic Benefit of Bone Marrow Stem Cell Transplantation after MI in Mice

et al. 2020

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“…Although we couldn't con rm myogenic differentiation of MSCs themselves in this study, IL-10 is also thought to play a role in the long-term engraftment and survival of MSCs in muscle tissue, resulting from association with surrounding myogenic stem/progenitor cell populations, such as satellite cells, skeletal muscle-MSCs, and broadipogenic progenitors (FAB) for muscle repair. Furthermore, myocardial infarction with CD271 + bonemarrow MSCs lowered expression of in ammatory cytokines and signi cantly increased pro-angiogenic VEGF [37]. CD271 + MSCs expressing IL-10 are also thought to enhance pro-angiogenic differentiation in injured tissue as a result of prolonged survival.…”

Section: Discussionmentioning

confidence: 99%

Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy

Kasahara

Kuraoka

Oda

et al. 2020

Preprint

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Background:Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and are immunosuppressive. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the IL-10 based anti-inflammatory properties and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.Methods:We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of AAV/IL-10 vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. The systemic treatment of IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to DMD patients. Results:In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hind-limb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into CXMDJ model resulted in long-term engraftment of cells, slightly increased serum levels of IL-10. IL-10-hDPSCs showed remarkably reduced expression of pro-inflammatory MCP-1, and upregulated stromal-derived factor-1 (SDF-1). In fact, MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability, and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in the IL-10-hDPSC-treated CXMDJ. Conclusions:In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles with physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy, through the beneficial IL-10 paracrine effects involving SDF-1.

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“…Bone regeneration comprises a series of complex and continuous physiological processes that can be divided into four stages: haematoma formation, fibrous callus formation, bone callus formation and bone shaping plus remodelling 7 . Numerous studies have shown that inflammatory responses and neovascularization are key factors for initiation of bone regeneration 8‐10 . Hausman et al 11 demonstrated that application of angiogenesis inhibitors to a rat model of femoral fracture inhibited fracture healing and led to atrophic nonunion.…”

Section: Introductionmentioning

confidence: 99%

Motivating role of type H vessels in bone regeneration

2020

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Coupling between angiogenesis and osteogenesis has an important role in both normal bone injury repair and successful application of tissue‐engineered bone for bone defect repair. Type H blood vessels are specialized microvascular components that are closely related to the speed of bone healing. Interactions between type H endothelial cells and osteoblasts, and high expression of CD31 and EMCN render the environment surrounding these blood vessels rich in factors conducive to osteogenesis and promote the coupling of angiogenesis and osteogenesis. Type H vessels are mainly distributed in the metaphysis of bone and densely surrounded by Runx2+ and Osterix+ osteoprogenitors. Several other factors, including hypoxia‐inducible factor‐1α, Notch, platelet‐derived growth factor type BB, and slit guidance ligand 3 are involved in the coupling of type H vessel formation and osteogenesis. In this review, we summarize the identification and distribution of type H vessels and describe the mechanism for type H vessel‐mediated modulation of osteogenesis. Type H vessels provide new insights for detection of the molecular and cellular mechanisms that underlie the crosstalk between angiogenesis and osteogenesis. As a result, more feasible therapeutic approaches for treatment of bone defects by targeting type H vessels may be applied in the future.

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Angiogenic Potential of Bone Marrow Derived CD133+ and CD271+ Intramyocardial Stem Cell Trans- Plantation Post MI

Cited by 23 publications

References 47 publications

Dose-Independent Therapeutic Benefit of Bone Marrow Stem Cell Transplantation after MI in Mice

Dose-Independent Therapeutic Benefit of Bone Marrow Stem Cell Transplantation after MI in Mice

Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy

Motivating role of type H vessels in bone regeneration

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