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Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine

Annals of Biomedical Engineering volume 44, pages 1325–1354 (2016)Cite this article

Abstract

Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

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Figure 1

Abbreviations

ABMSCT:

Autologous bone marrow derived mesenchymal stem cell transplantation

AC:

Articular cartilage

ACAN:

Aggrecan

ACh:

Articular chondrocyte

ACI:

Autologous chondrocyte implantation

ACTE:

Articular cartilage tissue engineering

ALP:

Alkaline phosphatase

AMSC:

Adipose derived mesenchymal stem cell

AMSCT:

Adipose mesenchymal stem cell transplantation

b:

Bovine

BMP:

Bone morphogenic protein

BMSC:

Bone marrow derived mesenchymal stem cell

C-ACI:

Col I/III-covered ACI

Ch:

Chondrocyte

CM:

Conditioned medium

Col:

Collagen

COMP:

Cartilage oligomeric matrix protein

Dex:

Dexamethasone

ECM:

Extracellular matrix

FGF:

Fibroblast growth factor

GAG:

Glycosaminoglycans

GF:

Growth factor

GFP:

Green fluorescent protein

h:

Human

IGF:

Insulin like growth factor

IHC:

Immunohistochemistry

iMSC:

Induced MSC w/specified GFs

M-ACI:

Matrix-induced ACI

MMP:

Matrix metallopeptidase

MSC:

Mesenchymal stem cell

OA:

Osteoarthritis

oaACh:

Osteoarthritic ACh

P#:

Passage number

P-ACI:

Periosteum-covered ACI

PD:

Population doubling

PTHrP:

Parathyroid hormone related peptide

Q-PCR:

Quantitative polymerase chain reaction

qRT-PCR:

Quantitative reverse transcription polymerase chain reaction

RT-PCR:

Real time polymerase chain reaction

SC:

Stem cell

SCID:

Severe combined immunodeficiency

TE:

Tissue engineering

TGF-β:

Transforming growth factor

TIMP:

Tissue inhibitor metallopeptidase

USDA:

United State Food & Drug Administration

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Acknowledgments

The authors gratefully acknowledge NSF support through CBET EAGER Award #1212573, Regeneron Pharmaceuticals, Inc., and USDA NIFA WN.P WNP00807 for salary support. The efforts of Professor Elizabeth Siler in editing this manuscript are appreciated.

Conflict of interest

The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Gene and Linda Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman, WA, 99164-6515, USA

    A. Nazempour & B. J. Van Wie

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  1. A. Nazempour
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  2. B. J. Van Wie
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Correspondence to B. J. Van Wie.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Nazempour, A., Van Wie, B.J. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine. Ann Biomed Eng 44, 1325–1354 (2016). https://doi.org/10.1007/s10439-016-1575-9

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  • DOI: https://doi.org/10.1007/s10439-016-1575-9

Keywords

  • Articular cartilage
  • Articular cartilage tissue engineering
  • Chondrocytes
  • Autologous chondrocyte implantation
  • Mesenchymal stem cells
  • Autologous mesenchymal stem cell transplantation
  • Co-culture of mesenchymal stem cells with articular chondrocytes