Meiling Zhou1, Jiaoya Xi1, Yaofeng Cheng2,3, Denglong Sun1, Peng Shu2, Shuiqing Chi4, Shuo Tian4, Shunan Ye5. 1. Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 2. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. 3. Department of Orthopedics, Suizhou Central Hospital, Hubei University of Medicine, Suizhou, Hubei, China. 4. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 5. Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China. shunany@126.com.
Abstract
BACKGROUND: Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for the osteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. METHODS: In the present study, the bone marrow samples of patients with ONFH (n = 16) and patients with the fracture of the femoral neck (n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFH patients (ONFH-BMSCs) were reprogrammed to iPSCs, following which the iPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups (n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after the establishment of the ONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of the femoral head necrosis area was analyzed after MSC transplantation. RESULTS: The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFH rat model revealed that the iPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in the necrosis region of the femoral head. CONCLUSION: Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in the necrosis area of the femoral head.
BACKGROUND: Cellular therapy based on mesenchymal stem cells (MSCs) is a promising novel therapeutic strategy for theosteonecrosis of the femoral head (ONFH), which is gradually becoming popular, particularly for early-stage ONFH. Nonetheless, the MSC-based therapy is challenging due to certain limitations, such as limited self-renewal capability of cells, availability of donor MSCs, and the costs involved in donor screening. As an alternative approach, MSCs derived from induced pluripotent stem cells (iPSCs), which may lead to further standardized-cell preparations. METHODS: In the present study, the bone marrow samples of patients with ONFH (n = 16) and patients with the fracture of the femoral neck (n = 12) were obtained during operation. The bone marrow-derived MSCs (BMSCs) were isolated by density gradient centrifugation. BMSCs of ONFHpatients (ONFH-BMSCs) were reprogrammed to iPSCs, following which theiPSCs were differentiated into MSCs (iPSC-MSCs). Forty adult male rats were randomly divided into following groups (n = 10 per group): (a) normal control group, (b) methylprednisolone (MPS) group, (c) MPS + BMSCs treated group, and (d) MPS + iPSC-MSC-treated group. Eight weeks after theestablishment of theONFH model, rats in BMSC-treated group and iPSC-MSC-treated group were implanted with BMSCs and iPSC-MSCs through intrabone marrow injection. Bone repair of thefemoral head necrosis area was analyzed after MSC transplantation. RESULTS: The morphology, immunophenotype, in vitro differentiation potential, and DNA methylation patterns of iPSC-MSCs were similar to those of normal BMSCs, while the proliferation of iPSC-MSCs was higher and no tumorigenic ability was exhibited. Furthermore, comparing the effectiveness of iPSC-MSCs and the normal BMSCs in an ONFHrat model revealed that theiPSC-MSCs was equivalent to normal BMSCs in preventing bone loss and promoting bone repair in thenecrosis region of the femoral head. CONCLUSION: Reprogramming can reverse the abnormal proliferation, differentiation, and DNA methylation patterns of ONFH-BMSCs. Transplantation of iPSC-MSCs could effectively promote bone repair and angiogenesis in thenecrosis area of the femoral head.
Entities:
Keywords:
Bone regeneration; Cell therapy; Human induced pluripotent stem cells; Mesenchymal stem cell; Osteonecrosis of the femoral head
Authors: Benjamin L Larson; Joni Ylostalo; Ryang H Lee; Carl Gregory; Darwin J Prockop Journal: Tissue Eng Part A Date: 2010-07-13 Impact factor: 3.845
Authors: Qingguo Zhao; Carl A Gregory; Ryang Hwa Lee; Roxanne L Reger; Lizheng Qin; Bo Hai; Min Sung Park; Nara Yoon; Bret Clough; Eoin McNeill; Darwin J Prockop; Fei Liu Journal: Proc Natl Acad Sci U S A Date: 2014-12-29 Impact factor: 11.205