Systemic Adult Stem Cell Therapy for Osteoporosis-Related Vertebral Compression Fractures
Vertebral compression fractures are the most common fractures associated with osteoporosis. Unfortunately there is no recommended treatment other than bed rest and pain medications. We propose to develop a new approach to accelerate bone repair that exploits systemic administration of MSCs and PTH. It has already been established that PTH alone can accelerate fracture repair in healthy animals by activating bone marrow MSCs. However, osteoporotic patients have decreased numbers of MSCs, and these are dysfunctional. Therefore, we hypothesized that an intravenous injection of MSCs combined with PTH administration would induce stem cell homing to vertebral defects followed by osteogenesis and defect repair. Toward this goal we induced osteopenia in athymic rats by ovarioectomy and low calcium diet, which resulted in 15-20% loss of bone mineral density. Our results showed that vertebral defects in osteopenic rats showed significantly more bone repair when treated with human MSCs and PTH, compared to the controls. Moreover, when we tracked labeled MSCs using optical and nuclear imaging systems, we could detect cell homing to the lumbar region of the animals. This study could provide an evidence base for future therapies that could revolutionize the treatment of vertebral and other complex fractures, especially in osteoporotic patients.
|MicroCT 3D images of osteoporotic rats with multiple vertebral defects, treated with PTH or a combination of PTH and hMSCs.|
Adipose Derived Stem Cells Reprogrammed to iPS Cells Can Be Efficiently Differentiated Back to MSCs
|Human ASC-derived iPS cells – fluorescent|
staining of pluripotency markers.
Mesenchymal stem cells are the ultimate source for tissue engineering of skeletal tissues and regeneration of various skeletal conditions. However, their availability and self-renewal ability is limited. Moreover, osteoporotic patients have decreased numbers of MSCs, and these are dysfunctional. The recent discoveries of the differentiated cells reprogramming opens new horizons in stem cell therapy and may be employed to overcome these challenges. We hypothesized that adipose derived stem cells (ASCs) could be reprogrammed to iPSCs and differentiated back to MSCs. ASCs were isolated from human adipose tissue and reprogrammed to a stable iPS clone that expressed pluripotent markers without chromosomal aberrations. Then the cells were directed toward mesenchymal lineages using short-term exposure of the embryonic bodies to TGFβ. The transition of the attached cells toward MSC stage was documented using FACS analysis against mesenchymal markers and was much more efficient than passive differentiation and outgrowth of MSCs from the embryonic bodies. Differentiation potential toward the three mesenchymal lineages was evaluated in vitro.
We could conclude that ASCs can be significantly expanded in the iPS stage and then efficiently reprogrammed back to the MSC stage.