Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect

Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal prog...

Full description

Saved in:
Bibliographic Details
Main Authors: Jun Li, Zeyu Huang, Bohua Li, Zhengdong Zhang, Lei Liu
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/5750967
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850104618422370304
author Jun Li
Zeyu Huang
Bohua Li
Zhengdong Zhang
Lei Liu
author_facet Jun Li
Zeyu Huang
Bohua Li
Zhengdong Zhang
Lei Liu
author_sort Jun Li
collection DOAJ
description Reconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.
format Article
id doaj-art-42cc9730d42a4c59a9cbdfdfe7edb78c
institution DOAJ
issn 1687-966X
1687-9678
language English
publishDate 2019-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-42cc9730d42a4c59a9cbdfdfe7edb78c2025-08-20T02:39:18ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/57509675750967Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone DefectJun Li0Zeyu Huang1Bohua Li2Zhengdong Zhang3Lei Liu4Department of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, ChinaDepartment of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, ChinaDepartment of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, ChinaDepartment of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, ChinaDepartment of Orthopedics, West China Hospital, Sichuan University, 37# Wainan Guoxue Road, Chengdu 610041, ChinaReconstruction of segmental bone defects poses a tremendous challenge for both orthopedic clinicians and scientists, since bone rehabilitation is requisite substantially and may be beyond the capacity of self-healing. Bone marrow mesenchymal stem cells (BMSCs) have been identified as an optimal progenitor cell source to facilitate bone repair since they have a higher ability for proliferation and are more easily accessible than mature osteoblastic cells. In spite of the potential of BMSCs in regeneration medicine, particularly for bone reconstruction, noteworthy limitations still remain in previous application of BMSCs, including the amount of cells that could be recruited, the compromised bone migration of grafted cells, reduced proliferation and osteoblastic differentiation ability, and likely tumorigenesis. Our current work demonstrates that BMSCs transplanted through the caudal vein can be mobilized by erythropoietin (EPO) to the bone defect area and participate in regeneration of new bone. Based on the histological analysis and micro-CT findings of this study, EPO can dramatically promote the effects on the osteogenesis and angiogenesis efficiency of BMSCs in vivo. Animals that underwent EPO+BMSC administration demonstrated a remarkable increase in new bone formation, tissue structure organization, new vessel density, callus formation, and bone mineral density (BMD) compared with the BMSCs alone and control groups. At the biomechanical level, we demonstrated that combing transplantation of EPO and BMSCs enhances bone defect reconstruction by increasing the strength of the diaphysis, making it less fragile. Therefore, combination therapy using EPO infusion and BMSC transplantation may be a new therapeutic strategy for the reconstruction of segmental bone defect.http://dx.doi.org/10.1155/2019/5750967
spellingShingle Jun Li
Zeyu Huang
Bohua Li
Zhengdong Zhang
Lei Liu
Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
Stem Cells International
title Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
title_full Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
title_fullStr Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
title_full_unstemmed Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
title_short Mobilization of Transplanted Bone Marrow Mesenchymal Stem Cells by Erythropoietin Facilitates the Reconstruction of Segmental Bone Defect
title_sort mobilization of transplanted bone marrow mesenchymal stem cells by erythropoietin facilitates the reconstruction of segmental bone defect
url http://dx.doi.org/10.1155/2019/5750967
work_keys_str_mv AT junli mobilizationoftransplantedbonemarrowmesenchymalstemcellsbyerythropoietinfacilitatesthereconstructionofsegmentalbonedefect
AT zeyuhuang mobilizationoftransplantedbonemarrowmesenchymalstemcellsbyerythropoietinfacilitatesthereconstructionofsegmentalbonedefect
AT bohuali mobilizationoftransplantedbonemarrowmesenchymalstemcellsbyerythropoietinfacilitatesthereconstructionofsegmentalbonedefect
AT zhengdongzhang mobilizationoftransplantedbonemarrowmesenchymalstemcellsbyerythropoietinfacilitatesthereconstructionofsegmentalbonedefect
AT leiliu mobilizationoftransplantedbonemarrowmesenchymalstemcellsbyerythropoietinfacilitatesthereconstructionofsegmentalbonedefect