Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

Abstract

Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis. The MSC transplantation promises to increase osteoblast differentiation and block osteoclast activation, and to rebalance bone formation and resorption. Preclinical investigations on MSC transplantation in the osteoporosis treatment provide evidences of enhancing osteogenic differentiation, increasing bone mineral density, and halting the deterioration of osteoporosis. Meanwhile, the latest techniques, such as gene modification, targeted modification and co-transplantation, are promising approaches to enhance the therapeutic effect and efficacy of MSCs. In addition, clinical trials of MSC therapy to treat osteoporosis are underway, which will fill the gap of clinical data. Although MSCs tend to be effective to treat osteoporosis, the urgent issues of safety, transplant efficiency and standardization of the manufacturing process have to be settled. Moreover, a comprehensive evaluation of clinical trials, including safety and efficacy, is still needed as an important basis for clinical translation.

Keywords: clinical trial; mesenchymal stem cells; osteoporosis; preclinical investigation; stem cell therapy.

FIGURE 1

Overview of the included articles for mesenchymal stem cell (MSC) transplantation in the treatment of osteoporosis. A, Flow diagram illustrating the study screening and inclusion process. B, Statistics for the numbers of publications in different years. C, Types of cells of the included articles. ASCs, adipose‐derived mesenchymal stem cells; BMMSCs, bone marrow mesenchymal stem cells; DPSCs, dental pulp stem cells; SHEDs, stem cells from human exfoliated deciduous teeth, PDSCs, placenta‐derived mesenchymal stem cells; TMSCs, tonsil‐derived mesenchymal stem cells; UCMSCs, umbilical cord blood mesenchymal stem cells

FIGURE 2

Mesenchymal stem cells (MSCs) in the pathogenesis of primary osteoporosis. Homing disorder results in a decreased number of MSCs in bone tissue under osteoporotic conditions. Impaired osteogenic ability and enhanced adipogenic ability of MSCs leads to less mature osteoblasts and more adipocytes. Senescence of MSCs further aggravates the imbalance of osteoblasts and adipocytes. In addition, abnormal activation of immune cells and impaired immunoregulatory ability of MSCs causes immune disorders in the bone niche, with altered cellular interactions and imbalanced paracrine secretion of many key signalling factors, such as RANK‐RANKL‐OPG axis. ↑indicates an increase in the number of cells/factors.↓indicates a decrease in the number of cells/factors. (+) represents the enhancement of the process. (−) represents the inhibition of the process. BMP2, bone morphogenetic protein 2; FGF, fibroblast growth factor; HSCs, hematopoietic stem cells; IGF, insulin‐like growth factor; OPG, osteoprotegerin; PDGF, platelet‐derived growth factor; PPARγ, peroxisome proliferator‐activated receptor γ; RANK, receptor activator of NF‐κB; RANKL, receptor activator of NF‐κB ligand

FIGURE 3

Preclinical studies on mesenchymal stem cell (MSC) transplantation in the treatment of osteoporosis