Advanced Therapy Medicinal Products: A Guide for Bone Marrow-derived MSC Application in Bone and Cartilage Tissue Engineering

Abstract

Millions of people worldwide suffer from trauma- or age-related orthopedic diseases such as osteoarthritis, osteoporosis, or cancer. Tissue Engineering (TE) and Regenerative Medicine are multidisciplinary fields focusing on the development of artificial organs, biomimetic engineered tissues, and cells to restore or maintain tissue and organ function. While allogenic and future autologous transplantations are nowadays the gold standards for both cartilage and bone defect repair, they are both subject to important limitations such as availability of healthy tissue, donor site morbidity, and graft rejection. Tissue engineered bone and cartilage products represent a promising and alternative approach with the potential to overcome these limitations. Since the development of Advanced Therapy Medicinal Products (ATMPs) such as TE products requires the knowledge of diverse regulation and an extensive communication with the national/international authorities, the aim of this review is therefore to summarize the state of the art on the clinical applications of human bone marrow-derived stromal cells for cartilage and bone TE. In addition, this review provides an overview of the European legislation to facilitate the development and commercialization of new ATMPs.

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

“…Recent advances have demonstrated that inducing the bone formation to restore the normal bone homeostasis is efficient for osteoporosis treatment 1 . Although osteogenesis induced by biological materials has gained much attention, classic methods are still applied in the studies of osteogenic differentiation of MSCs 2‐5 . Human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs), a stem cell population, possess many advantages relative to other cell sources, 6 including easily isolated, abundantly supply, 7 low immune rejection, 8 self‐renewing ability and multipotency 9 .…”

Advancing Frontiers in Bone Bioprinting

“…Other related challenges include limited autologous cell supply, difference in the outcome of stem cell therapy between patients, and the risk of rejection and disease transmission through allogenic stem cell therapy . There are also issues related to applications, such as the complex CMF skeleton, concerns about the unregulated clinical use of stem cells, and regulatory approval aspects …”

Emerging role of exosomes in craniofacial and dental applications

“…Craniofacial bone defects after trauma, infection, tumor resection and congenital deformities lead to different degrees of deformity and dysfunction in patients. The traditional clinical approaches for repair involve autologous, allogeneic bone grafting, and distraction osteogenesis, which may provide positive results but suffer from shortcomings, including donor site morbidity, immune complications, and cosmetic concerns 57 . Bone tissue engineering has emerged as a promising solution to overcome these shortcomings with the controlled application of cells, combined with biocompatible materials, for therapy 58 .…”