Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration
1046-2023/ 2015 The Authors. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.ymeth.2015.09.015
Stephen M. Richardson a,1, Gauthaman Kalamegam b,1, Peter N. Pushparaj b, Csaba Matta c, Adnan Memic d, Ali Khademhosseini e,f,g,h, Reza Mobasheri i, Fabian L. Poletti i, Judith A. Hoyland a,k, Ali Mobasheri c,j,b,⇑
Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enor-mous costs for health and social care systems. Development of cell-based therapies is rapidly proliferat-ing in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that caneffectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymalstem cells (MSCs) isolated from bone marrow (BM-MSCs), adipose tissue (AD-MSCs) and umbilical cord(UC-MSCs) show considerable promise for use in cartilage and intervertebral disc (IVD) repair. Thisreview article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of therising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitorcells and specifically focus on umbilical cord/Wharton’s jelly derived MSCs and examine their potentialfor regenerative applications. We also summarize key components of the molecular machinery and sig-naling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and bio-materials for articular cartilage and IVD regeneration. This review explores the exciting opportunitiesafforded by MSCs and discusses the challenges associated with cartilage and IVD repair and regeneration.There are still many technical challenges associated with isolating, expanding, differentiating, andpre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, theprospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondropro-genitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significantbreakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.
MSC-based therapies offer huge potential to revolutionize thetreatment of cartilage defects and IVD degeneration and the advances discussed in this manuscript highlight the progress beingmade toward clinical translation of such approaches. However, awide range of technical hurdles and conceptual challenges muststill be overcome as research progresses in this exciting and rapidlyexpanding field. There are still many technical challenges associ-ated with isolating, expanding, differentiating, and pre-conditioning MSCs for subsequent implantation into degeneratejoints and the spine. The physiological microenvironment of bothdiseased joints and intervertebral discs is likely to be hypoxic,acidic, deprived of nutrients, and exposed to higher than normalconcentrations of pro-inflammatory cytokines and reactive oxygenspecies. Furthermore, MSCs may be exposed to abnormal physicalloads in anatomical structures that have already been biomechan-ically compromised. Thus future regenerative medicine strategieswill need to address these remaining concerns.