Concise review: unraveling stem cell cocultures in regenerative medicine: which cell interactions steer cartilage regeneration and how?
Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartilage regeneration in vitro and in vivo. However, there is considerable debate regarding the mechanisms and cellular interactions that lead to chondrogenesis in these models. This review, which included 52 papers, provides a systematic overview of the data presented in the literature and tries to elucidate the mechanisms that lead to chondrogenesis in stem cell cocultures with cartilage cells. It could serve as a basis for research groups and clinicians aiming at designing and implementing combined cellular technologies for single-stage cartilage repair and treatment or prevention of OA.
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Tommy S
TS
de Windt
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Jeanine A A
JA
Hendriks
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Xing
X
Zhao
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Lucienne A
LA
Vonk
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Laura B
LB
Creemers
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Wouter J A
WJ
Dhert
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands.
Mark A
MA
Randolph
Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands; CellCoTec, Bilthoven, The Netherlands; Laboratory of Musculoskeletal Tissue Engineering, Department of Orthopaedic Surgery, and Division of Plastic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA; Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands; MIRA Institute for Biotechnology and Technical Medicine, University Twente, Enschede, The Netherlands d.saris@umcutrecht.nl.
Daniel B F
DB
Saris
D000818:Animals; D002356:Cartilage / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D002450:Cell Communication; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D020219:Chondrogenesis; D018920:Coculture Techniques; D006801:Humans; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D012038:Regeneration; D044968:Regenerative Medicine / Q000379:methods*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
Bone marrow stromal cells; Cellular therapy; Chondrogenesis; Clinical translation; Marrow stromal stem cells; Mesenchymal stem cells; Skeleton