The clinical potential of articular cartilage-derived progenitor cells: a systematic review

Abstract

Over the past two decades, evidence has emerged for the existence of a distinct population of endogenous progenitor cells in adult articular cartilage, predominantly referred to as articular cartilage-derived progenitor cells (ACPCs). This progenitor population can be isolated from articular cartilage of a broad range of species, including human, equine, and bovine cartilage. In vitro, ACPCs possess mesenchymal stromal cell (MSC)-like characteristics, such as colony forming potential, extensive proliferation, and multilineage potential. Contrary to bone marrow-derived MSCs, ACPCs exhibit no signs of hypertrophic differentiation and therefore hold potential for cartilage repair. As no unique cell marker or marker set has been established to specifically identify ACPCs, isolation and characterization protocols vary greatly. This systematic review summarizes the state-of-the-art research on this promising cell type for use in cartilage repair therapies. It provides an overview of the available literature on endogenous progenitor cells in adult articular cartilage and specifically compares identification of these cell populations in healthy and osteoarthritic (OA) cartilage, isolation procedures, in vitro characterization, and advantages over other cell types used for cartilage repair. The methods for the systematic review were prospectively registered in PROSPERO (CRD42020184775).

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration

“…Termed articular cartilage-derived progenitor cells (ACPCs), these cells most likely reside in the superficial zone in healthy cartilage and will migrate toward the sites of cartilage injury ( Grogan et al, 2009 ; Williams et al, 2010 ). These cells show similar markers to those of MSCs (CD90, CD105, CD73, and CD166) ( Rikkers et al, 2022 ), possibly distinguished phenotypically by an increased expression of CD44 and enhanced expression of fibronectin and integrin-α5β1 ( Dowthwaite et al, 2004 ; Levato et al, 2017 ), suggesting a unique progenitor cell population. Correspondingly, OA joint-derived ACPCs were shown to form more colonies in vitro compared to those from healthy human cartilage, suggesting greater proliferation capacity with increasing OA severity ( Wang et al, 2020 ; Rikkers et al, 2022 ).…”

“…These cells show similar markers to those of MSCs (CD90, CD105, CD73, and CD166) ( Rikkers et al, 2022 ), possibly distinguished phenotypically by an increased expression of CD44 and enhanced expression of fibronectin and integrin-α5β1 ( Dowthwaite et al, 2004 ; Levato et al, 2017 ), suggesting a unique progenitor cell population. Correspondingly, OA joint-derived ACPCs were shown to form more colonies in vitro compared to those from healthy human cartilage, suggesting greater proliferation capacity with increasing OA severity ( Wang et al, 2020 ; Rikkers et al, 2022 ). An increase in progenitor markers, such as CD271 ( Wang et al, 2020 ), CD105 ( Zhang et al, 2016 ), and VCAM ( Grogan et al, 2009 ) at sites of trauma or in OA cartilage were also observed.…”

“…Perhaps the most obvious endogenous progenitor cell population for cartilage repair is that which resides within cartilage itself, as recently reviewed by Rikkers et al( 2022 ). Termed articular cartilage-derived progenitor cells (ACPCs), these cells most likely reside in the superficial zone in healthy cartilage and will migrate toward the sites of cartilage injury ( Grogan et al, 2009 ; Williams et al, 2010 ).…”

“…An increase in progenitor markers, such as CD271 ( Wang et al, 2020 ), CD105 ( Zhang et al, 2016 ), and VCAM ( Grogan et al, 2009 ) at sites of trauma or in OA cartilage were also observed. Though these data suggest the involvement of ACPCs in cartilage repair, in vivo models outlining corresponding mechanisms are lacking, leaving the role(s) of these progenitor cells in cartilage repair and homeostasis unclear at this time ( Rikkers et al, 2022 ).…”

Roles of Cartilage-Resident Stem/Progenitor Cells in Cartilage Physiology, Development, Repair and Osteoarthritis

“…CSPCs are characterized by the traditional MSC markers individually or in combination, including CD105, CD73, CD54, CD106, CD166, CD9, CD90, CD146, CD44e, and CD271 ( Figure 1 B) [ 24 , 33 , 36 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Additionally, some studies have distinguished CSPCs in articular cartilage more specifically by using markers such as laminin, integrin-α5β1, Jagged, Notch-1, Notch-2, Delta, and STRO 1 [ 42 , 45 , 48 , 57 , 58 , 59 ]. However, none of the above studies identified a CSPC-specific marker to directly identify and distinguish them from MSCs and chondrocytes either in vitro or in vivo.…”