3D Reconstitution of Nerve–Blood Vessel Networks Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet Pellets

Tamaki, Toru; Soeda, Shinji; Hashimoto, Hiroyuki; Saito, Kosuke; Sakai, Akihiro; Nakajima, Nobuyuki; Masuda, Maki; Fukunishi, Nahoko; Uchiyama, Yoshiyasu; Terachi, Toshiro; Mochida, Joji

doi:10.2217/rme.13.30

Cited by 14 publications

(36 citation statements)

References 35 publications

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“…Interestingly, we found that CD31‐positive cells also expressed GFP in both transverse mid‐segment and longitudinal sections (Figure ). The capacity of MDSCs to promote angiogenesis in vivo through growth factor secretion and differentiation into endothelial cells has been suggested in previous studies . Our results confirmed that grafted MDSCs turn into vascular endothelial cells forming newborn vessels to benefit injured nerve regeneration.…”

Section: Discussionsupporting

confidence: 89%

Grafted muscle‐derived stem cells promote the therapeutic efficiency of epimysium conduits in mice with peripheral nerve gap injury

Chen

Feng

et al. 2019

Artificial Organs

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Our research aimed to build allogeneic artificial conduits with epimysium and muscle-derived stem cells (MDSCs) from the skeletal muscle of mice. We applied the conduit to repair peripheral nerve defects and estimated the effectiveness of the repair process. In the research, we prepared epimysium conduits with lumens to bridge repair a 5-mm-long sciatic nerve defect from C57 wild-type mice and then transplanted green fluorescent protein (GFP)-MDSCs and Matrigel suspensions into the conduit. Histological and functional assessments were performed 4 and 8 weeks after surgery. The tissue-engineered conduit from muscle effectively repaired the nerve defect, while the group with GFP-MDSCs showed improved histological examinations and functional assessments, and the newborn nerves highly expressed GFP. As the results suggested, autologous epimysium conduits represent a reliable method to repair peripheral nerve defects, and the addition of MDSCs promote the effectiveness of differentiating into multiple lineages. Our research simultaneously demonstrated the myogenic, neurogenic, and angiogenic potential of MDSCs in vivo for the first time. K E Y W O R D S microsurgery, peripheral nerve injury, regenerative medicine, stem cells, tissue engineering | E215 XU et al.

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Section: Discussionsupporting

confidence: 89%

Grafted muscle‐derived stem cells promote the therapeutic efficiency of epimysium conduits in mice with peripheral nerve gap injury

Chen

Feng

et al. 2019

Artificial Organs

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“…Cell differentiation into Schwann cells, perineurial/endoneurial cells, vascular endothelial cells and pericytes, and fibroblasts were mainly observed. Immunoelectron microscopy was performed as described previously [8, 9, 16, 17, 19, 21]. Consequently, the HNA-positive cells were detected as cells having dark nuclei because of products that reacted with DAB (black dots) in the immunoelectron micrograph.…”

Section: Methodsmentioning

confidence: 99%

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

et al. 2016

Self Cite

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Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8–12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk-SCs may be a practical source for autologous stem cell therapy following severe peripheral nerve injury.

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“…Since nephrons are largely of mesenchymal origin and stromal cells are of crucial importance for signaling leading to the differentiation of both nephrons and collecting ducts, MSCs are undifferentiated adult cells and may be isolated from bone marrow, umbilical cord, adipose tissue, placenta, synovium, and skeletal muscle [10–14]. They are characterized by three main criteria: (a) the ability to differentiate into osteoblasts, adipocytes, and chondroblasts in vitro ; (b) the expression of surface markers CD73, CD90, and CD105; lack of expression of haematopoietic markers including CD34 and CD45; (c) plastic adherence in culture [15].…”

Section: Mesenchymal Stem Cells (Mscs)mentioning

confidence: 99%

The Regulation of Inflammatory Mediators in Acute Kidney Injury via Exogenous Mesenchymal Stem Cells

Zhu

2014

Mediators of Inflammation

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Acute kidney injury (AKI) remains to be an independent risk factor for mortality and morbidity. Inflammation is believed to play a major role in the pathophysiology of AKI. Exogenous mesenchymal stem cells (MSCs) are now under extensive investigation as a potential therapy for AKI. Various preclinical studies indicated the beneficial effects of MSCs in alleviating renal injury and accelerating tissue repair. However the mechanisms responsible for these effects are incompletely understood. In the recent years, anti-inflammatory/immunoregulatory properties of MSCs have become one of the important issues in the treatment of AKI. This review will summarize the current literature on the regulation of inflammatory mediators via exogenous MSCs contributing to the recovery from AKI.

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3D Reconstitution of Nerve–Blood Vessel Networks Using Skeletal Muscle-Derived Multipotent Stem Cell Sheet Pellets

Abstract: These results indicate that the vigorous skeletal myogenic potential of Sk-MSCs was clearly reduced in the sheet pellet preparation and this method may be a useful adjuvant for nerve-vascular regeneration in various tissue engineering applications.

Cited by 14 publications

References 35 publications

Grafted muscle‐derived stem cells promote the therapeutic efficiency of epimysium conduits in mice with peripheral nerve gap injury

Grafted muscle‐derived stem cells promote the therapeutic efficiency of epimysium conduits in mice with peripheral nerve gap injury

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

The Regulation of Inflammatory Mediators in Acute Kidney Injury via Exogenous Mesenchymal Stem Cells

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