Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve
Abstract Background Neurovascular unit restoration is crucial for nerve regeneration, especially in critical gaps of injured peripheral nerve. Multipotent vascular stem cells (MVSCs) harvested from an adult blood vessel are involved in vascular remodeling; however, the therapeutic benefit for nerve...
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doaj-16211c15ac024bcb9a819117401107f52020-11-25T03:24:24ZengBMCStem Cell Research & Therapy1757-65122019-08-011011910.1186/s13287-019-1317-7Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerveChing-Wen Huang0Yuan-Yu Hsueh1Wen-Chin Huang2Shyam Patel3Song Li4Department of Bioengineering, University of CaliforniaDivision of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaAbstract Background Neurovascular unit restoration is crucial for nerve regeneration, especially in critical gaps of injured peripheral nerve. Multipotent vascular stem cells (MVSCs) harvested from an adult blood vessel are involved in vascular remodeling; however, the therapeutic benefit for nerve regeneration is not clear. Methods MVSCs were isolated from rats expressing green fluorescence protein (GFP), expanded, mixed with Matrigel matrix, and loaded into the nerve conduits. A nerve autograft or a nerve conduit (with acellular matrigel or MVSCs in matrigel) was used to bridge a transected sciatic nerve (10-mm critical gap) in rats. The functional motor recovery and cell fate in the regenerated nerve were investigated to understand the therapeutic benefit. Results MVSCs expressed markers such as Sox 17 and Sox10 and could differentiate into neural cells in vitro. One month following MVSC transplantation, the compound muscle action potential (CMAP) significantly increased as compared to the acellular group. MVSCs facilitated the recruitment of Schwann cell to regenerated axons. The transplanted cells, traced by GFP, differentiated into perineurial cells around the bundles of regenerated myelinated axons. In addition, MVSCs enhanced tight junction formation as a part of the blood-nerve barrier (BNB). Furthermore, MVSCs differentiated into perivascular cells and enhanced microvessel formation within regenerated neurovascular bundles. Conclusions In rats with peripheral nerve injuries, the transplantation of MVSCs into the nerve conduits improved the recovery of neuromuscular function; MVSCs differentiated into perineural cells and perivascular cells and enhanced the formation of tight junctions in perineural BNB. This study demonstrates the in vivo therapeutic benefit of adult MVSCs for peripheral nerve regeneration and provides insight into the role of MVSCs in BNB regeneration.http://link.springer.com/article/10.1186/s13287-019-1317-7Multipotent vascular stem cellStem cell therapyPeripheral nerve regenerationBlood-nerve barrier |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ching-Wen Huang Yuan-Yu Hsueh Wen-Chin Huang Shyam Patel Song Li |
spellingShingle |
Ching-Wen Huang Yuan-Yu Hsueh Wen-Chin Huang Shyam Patel Song Li Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve Stem Cell Research & Therapy Multipotent vascular stem cell Stem cell therapy Peripheral nerve regeneration Blood-nerve barrier |
author_facet |
Ching-Wen Huang Yuan-Yu Hsueh Wen-Chin Huang Shyam Patel Song Li |
author_sort |
Ching-Wen Huang |
title |
Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
title_short |
Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
title_full |
Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
title_fullStr |
Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
title_full_unstemmed |
Multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
title_sort |
multipotent vascular stem cells contribute to neurovascular regeneration of peripheral nerve |
publisher |
BMC |
series |
Stem Cell Research & Therapy |
issn |
1757-6512 |
publishDate |
2019-08-01 |
description |
Abstract Background Neurovascular unit restoration is crucial for nerve regeneration, especially in critical gaps of injured peripheral nerve. Multipotent vascular stem cells (MVSCs) harvested from an adult blood vessel are involved in vascular remodeling; however, the therapeutic benefit for nerve regeneration is not clear. Methods MVSCs were isolated from rats expressing green fluorescence protein (GFP), expanded, mixed with Matrigel matrix, and loaded into the nerve conduits. A nerve autograft or a nerve conduit (with acellular matrigel or MVSCs in matrigel) was used to bridge a transected sciatic nerve (10-mm critical gap) in rats. The functional motor recovery and cell fate in the regenerated nerve were investigated to understand the therapeutic benefit. Results MVSCs expressed markers such as Sox 17 and Sox10 and could differentiate into neural cells in vitro. One month following MVSC transplantation, the compound muscle action potential (CMAP) significantly increased as compared to the acellular group. MVSCs facilitated the recruitment of Schwann cell to regenerated axons. The transplanted cells, traced by GFP, differentiated into perineurial cells around the bundles of regenerated myelinated axons. In addition, MVSCs enhanced tight junction formation as a part of the blood-nerve barrier (BNB). Furthermore, MVSCs differentiated into perivascular cells and enhanced microvessel formation within regenerated neurovascular bundles. Conclusions In rats with peripheral nerve injuries, the transplantation of MVSCs into the nerve conduits improved the recovery of neuromuscular function; MVSCs differentiated into perineural cells and perivascular cells and enhanced the formation of tight junctions in perineural BNB. This study demonstrates the in vivo therapeutic benefit of adult MVSCs for peripheral nerve regeneration and provides insight into the role of MVSCs in BNB regeneration. |
topic |
Multipotent vascular stem cell Stem cell therapy Peripheral nerve regeneration Blood-nerve barrier |
url |
http://link.springer.com/article/10.1186/s13287-019-1317-7 |
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