Stromal cells and stem cells in clinical bone regeneration

Abstract

Stem-cell-mediated bone repair has been used in clinical trials for the regeneration of large craniomaxillofacial defects, to slow the process of bone degeneration in patients with osteonecrosis of the femoral head and for prophylactic treatment of distal tibial fractures. Successful regenerative outcomes in these investigations have provided a solid foundation for wider use of stromal cells in skeletal repair therapy. However, employing stromal cells to facilitate or enhance bone repair is far from being adopted into clinical practice. Scientific, technical, practical and regulatory obstacles prevent the widespread therapeutic use of stromal cells. Ironically, one of the major challenges lies in the limited understanding of the mechanisms via which transplanted cells mediate regeneration. Animal models have been used to provide insight, but these models largely fail to reproduce the nuances of human diseases and bone defects. Consequently, the development of targeted approaches to optimize cell-mediated outcomes is difficult. In this Review, we highlight the successes and challenges reported in several clinical trials that involved the use of bone-marrow-derived mesenchymal or adipose-tissue-derived stromal cells. We identify several obstacles blocking the mainstream use of stromal cells to enhance skeletal repair and highlight technological innovations or areas in which novel techniques might be particularly fruitful in continuing to advance the field of skeletal regenerative medicine.

Induction of steroidogenic cells from adult stem cells and pluripotent stem cells [Review]

“…Owing to their mulitipotency, paracrine potential and immune tolerance properties following transplantation, they are widely applicable in the field of tissue regeneration [30][31][32]. In fact, successful clinical therapeutic interventions using MSCs have been made in bone regeneration [33] and cardiac repair [34,35], to name a few.…”

Comparative study of neural differentiation of bone marrow mesenchymal stem cells by different induction methods

“…The interest in studying this multipotent cell population largely derives from its advantages (Friedenstein et al, 1987). For instance, MSCs can be easily harvested for autologous transplantation and do not involve ethical issues (Grayson et al, 2015). Although both undifferentiated and differentiated MSCs have been used for cell transplantation in neurological diseases, in vitro differentiation prior to transplantation may be safer than in vivo implantation (Yaghoobi et al, 2008).…”

Editor’s Spotlight/Take 5: Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head

“…Although less is known about adipose-derived MSCs than about bonemarrow-derived MSCs, the former seem especially promising for certain applications. Though adipose-derived cells appear to be less chondrogenic than bone-marrow-derived MSCs, adiposederived MSCs possess an exciting ability to regenerate bone [2], and, as we see in this issue of CORR 1 , perhaps to begin to move us towards new therapies for one of the most treatment-resistant conditions in all of orthopaedics: Osteonecrosis.…”