title: 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.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 400 North Broadway, Baltimore, MD 21205, USA.
authors.forename: Warren L
authors.initials: WL
authors.lastname: Grayson
authors.affiliation: Centre for Stem Cell Research and Regenerative Medicine, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Bunnell
authors.affiliation: Centre for Stem Cell Research and Regenerative Medicine, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Martin
authors.affiliation: Centre for Stem Cell Research and Regenerative Medicine, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA.
authors.forename: Trivia
authors.initials: T
authors.lastname: Frazier
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 400 North Broadway, Baltimore, MD 21205, USA.
authors.forename: Ben P
authors.initials: BP
authors.lastname: Hung
authors.affiliation: Centre for Stem Cell Research and Regenerative Medicine, 1430 Tulane Avenue, SL-99, New Orleans, LA 70112, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000628:therapy*; D001851:Bone Diseases, Metabolic / Q000628:therapy; D001861:Bone Regeneration; D002986:Clinical Trials as Topic; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology*; D014945:Wound Healing