Journal Article

Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age‐Related Osteoporosis

Kiernan, Jeffrey, Davies, John E., Grynpas, Marc D., Stanford, William L., Hu, Sally

2016

Overview

The injection of minimally expanded exogenous mesenchymal stromal cells (MSCs) into a mouse model of human age‐related osteoporosis led to long‐term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and sustained microarchitectural competence, establishing proof of concept that MSC transplantation may be used to prevent or treat human age‐related osteoporosis. Age‐related osteoporosis is driven by defects in the tissue‐resident mesenchymal stromal cells (MSCs), a heterogeneous population of musculoskeletal progenitors that includes skeletal stem cells. MSC decline leads to reduced bone formation, causing loss of bone volume and the breakdown of bony microarchitecture crucial to trabecular strength. Furthermore, the low‐turnover state precipitated by MSC loss leads to low‐quality bone that is unable to perform remodeling‐mediated maintenance—replacing old damaged bone with new healthy tissue. Using minimally expanded exogenous MSCs injected systemically into a mouse model of human age‐related osteoporosis, we show long‐term engraftment and markedly increased bone formation. This led to improved bone quality and turnover and, importantly, sustained microarchitectural competence. These data establish proof of concept that MSC transplantation may be used to prevent or treat human age‐related osteoporosis. Significance This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age‐related osteoporosis display long‐term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age‐related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age‐related osteoporosis.

• Publisher: AlphaMed Press,Oxford University Press
• Subject: Age / Animals / Anisotropy / Ataxin-1 - deficiency / Ataxin-1 - genetics / Biomarkers - metabolism / Bone and Bones - metabolism / Bone and Bones - pathology / Bone and Bones - physiopathology / Bone growth / Bone loss / Bone marrow / Bone turnover / Cell Separation - methods / Cell Survival / Cells, Cultured / Clinical trials / Connectivity / Data analysis / Disease Models, Animal / Graft Survival / Laboratories / Mesenchymal stem cell / Mesenchymal Stem Cell Transplantation / Mesenchymal Stem Cells - metabolism / Mesenchyme / Mice, Knockout / Osteogenesis / Osteoporosis / Osteoporosis - genetics / Osteoporosis - metabolism / Osteoporosis - pathology / Osteoporosis - physiopathology / Osteoporosis - surgery / Phenotype / Sca‐1 / Stem cell transplantation / Stem cells / Stromal cells / Studies / Time Factors / Tissue Engineering and Regenerative Medicine / Tissue‐specific stem cells / Transplantation / Transplants & implants