American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies

Abstract

Cell‐based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell‐based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web‐based marketing and patient testimonials supporting cell‐based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell‐based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell‐based therapies. The Task Force was charged with defining the state‐of‐the art in cell‐based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell‐based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2019 American Society for Bone and Mineral Research.

FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair

“…This suggests that PCs could be beneficial in cell-based approaches to treat pseudarthrosis, given their positive effect on the very dynamic process of bone healing. Furthermore, in a cell-based therapy setting, it is generally accepted that long-term integration of transplanted cells is needed for efficient treatment ( O'Keefe et al., 2020b ; O'Keefe et al., 2020a ). Our results illustrate that transient integration of PCs may be sufficient to correct a skeletal repair disorder.…”

Success Criteria for Preclinical Testing of Cell-Instructive Hydrogels for Tendon Regeneration

“…Hydrogels, including collagen- 19 and extracellular matrix (ECM)-based 20 gels, are used as carriers to guide and deliver stem cells. However, the clinical efficacy and the role of transplanted cells in tendon repair remains ambiguous 21 . Promising new synthetic hydrogels may circumvent the need for stem cell delivery if these materials contain deliberately designed cell-instructive cues, such as cell integrin-binding domains, fibrous ECM-mimetic peptides, tunable mechanical properties, and matrix metalloprotease (MMP)-degradable linker peptides 17,22 .…”

Much-Needed Clarification and Guidance on Cell-Based Therapies for Musculoskeletal Disorders

“…(1) Early descriptions of "the mesenchymal stem cell" by Friedenstein (2) and colleagues and later by Caplan (3) characterized these progenitors as a nonhematopoietic cell expanded by in vitro culture with the ability to self-renew and differentiate along multiple lineages. (1) Early descriptions of "the mesenchymal stem cell" by Friedenstein (2) and colleagues and later by Caplan (3) characterized these progenitors as a nonhematopoietic cell expanded by in vitro culture with the ability to self-renew and differentiate along multiple lineages.…”

“…W ithin the last 30 years, there have been many advancements within the field of stem cell biology, and controversies regarding their clinical implementation make the joint American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) Task Force by O'Keefe and colleagues especially timely. (1) Early descriptions of "the mesenchymal stem cell" by Friedenstein (2) and colleagues and later by Caplan (3) characterized these progenitors as a nonhematopoietic cell expanded by in vitro culture with the ability to self-renew and differentiate along multiple lineages. Since then, our understanding and ability to isolate pure populations of tissue-resident stem cells has allowed for the more accurate determination of key cellular signaling pathways.…”