Tissue specific stem/progenitor cells for cartilage tissue engineering: A systematic review of the literature

Abstract

Cartilage derived stem/progenitor cells (CSPCs) have been isolated from a variety of cartilage sources and are suggested to have high chondrogenic potential. However, their role in cartilage engineering has not been well described, in particular, compared to other more widely used cell types such as differentiated chondrocytes and nontissue-specific mesenchymal stem cells (MSCs). The authors performed a systematic review of literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines [Web of Science (Web of Science Core Collection, BIOSIS Citation Index, KCI-Korean Journal Database, MEDLINE, SciELO Citation Index), PubMed, and Embase] from January 1947 to November 2017, to evaluate CSPC isolation, their characterization, and cartilage regeneration. Two investigators independently reviewed all studies and extracted the data against standardized inclusion/exclusion criteria. A total of 1189 studies were identified, 65 of which met the inclusion criteria, consisting of 69 reports on CSPC isolation from articular (n = 35), intervertebral disk (11), auricular (n = 10), meniscal (n = 5), nasoseptal (n = 5), tracheal (n = 2), and costal (n = 1) cartilages. Despite the heterogeneity in isolation methods, 75% of studies found CSPCs to have trilineage differentiation potential, with consistent but nonspecific cell surface marker expression profiles, being positive for the recognized MSC markers CD90, CD105, CD44, CD166, CD73, and CD29 and negative for hematopoietic markers CD34 and CD45. Four cartilage regenerative outcomes were assessed: chondrogenic gene and protein expression (quantitative polymerase chain reaction, histology, immunohistochemistry, and biochemistry), imaging and structural characterization (gross appearance, scanning electron microscopy, and transmission electron microscopy) and biomechanical testing. CSPCs have been used for cartilage repair in animal models with excellent outcomes that are comparable to chondrocytes and superior to MSCs from unrelated tissue sources. The current review concludes that CSPCs represent a promising cell source for cartilage tissue engineering, but there is currently no consensus on specific cell surface markers or isolation protocols.