title: Mesenchymal stem cells in regenerative medicine: Focus on articular cartilage and intervertebral disc regeneration.
abstract: Musculoskeletal disorders represent a major cause of disability and morbidity globally and result in enormous costs for health and social care systems. Development of cell-based therapies is rapidly proliferating in a number of disease areas, including musculoskeletal disorders. Novel biological therapies that can effectively treat joint and spine degeneration are high priorities in regenerative medicine. Mesenchymal stem 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. This review article focuses on stem cell-based therapeutics for cartilage and IVD repair in the context of the rising global burden of musculoskeletal disorders. We discuss the biology MSCs and chondroprogenitor cells and specifically focus on umbilical cord/Wharton's jelly derived MSCs and examine their potential for regenerative applications. We also summarize key components of the molecular machinery and signaling pathways responsible for the control of chondrogenesis and explore biomimetic scaffolds and biomaterials for articular cartilage and IVD regeneration. This review explores the exciting opportunities afforded 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, and pre-conditioning MSCs for subsequent implantation into degenerate joints and the spine. However, the prospect of combining biomaterials and cell-based therapies that incorporate chondrocytes, chondroprogenitors and MSCs leads to the optimistic view that interdisciplinary approaches will lead to significant breakthroughs in regenerating musculoskeletal tissues, such as the joint and the spine in the near future.
authors.affiliation: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom. Electronic address: s.richardson@manchester.ac.uk.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Richardson
authors.affiliation: Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: kgauthaman@kau.edu.sa.
authors.forename: Gauthaman
authors.initials: G
authors.lastname: Kalamegam
authors.affiliation: Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: peter.n.pushparaj@gmail.com.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Pushparaj
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom. Electronic address: c.matta@surrey.ac.uk.
authors.forename: Csaba
authors.initials: C
authors.lastname: Matta
authors.affiliation: Center for Nanotechnology and Department of Physics, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: amemic@gmail.com.
authors.forename: Adnan
authors.initials: A
authors.lastname: Memic
authors.affiliation: Biomaterials Innovation Research Centre and Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA; Department of Bioindustrial Technologies, College of Animal Bioscience and Technology, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea. Electronic address: alik@rics.bwh.harvard.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Khademhosseini
authors.affiliation: Imperial Healthcare NHS Trust, Department of Orthopaedics, Salton House, St. Mary's Hospital, London W2 1NY, United Kingdom. Electronic address: reza.mobasheri@imperial.nhs.uk.
authors.forename: Reza
authors.initials: R
authors.lastname: Mobasheri
authors.affiliation: Imperial Healthcare NHS Trust, Department of Orthopaedics, Salton House, St. Mary's Hospital, London W2 1NY, United Kingdom. Electronic address: Fabian.poletti@imperial.nhs.uk.
authors.forename: Fabian L
authors.initials: FL
authors.lastname: Poletti
authors.affiliation: Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, Faculty of Medical and Human Sciences, The University of Manchester, Manchester M13 9PT, United Kingdom; NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academic Health Science Centre, Manchester M13 9WL, United Kingdom. Electronic address: judith.a.hoyland@manchester.ac.uk.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hoyland
authors.affiliation: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom; Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Arthritis Research UK Pain Centre, Medical Research Council and Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom; Center of Excellence in Genomic Medicine Research (CEGMR), King Fahd Medical Research Center (KFMRC), Faculty of Applied Medical Sciences, King AbdulAziz University, Jeddah 21589, Saudi Arabia. Electronic address: a.mobasheri@surrey.ac.uk.
authors.forename: Ali
authors.initials: A
authors.lastname: Mobasheri
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000502:physiology*; D006801:Humans; D007403:Intervertebral Disc / Q000502:physiology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D012038:Regeneration; D044968:Regenerative Medicine; D015398:Signal Transduction; D023822:Tissue Engineering; D059631:Wharton Jelly / Q000166:cytology
keywords: Adipose-derived stem cell (AD-MSC); Articular cartilage; Biological therapy; Cellular therapy; IVD degeneration; Intervertebral disc (IVD); Low back pain (LBP); Mesenchymal stem cell (MSC); Osteoarthritis (OA); Regenerative medicine; Tissue engineering; Umbilical cord; Wharton’s Jelly stem cell (WJSC)