Engineered cartilage utilizing fetal cartilage-derived progenitor cells for cartilage repair

Abstract

The aim of this study was to develop a fetal cartilage-derived progenitor cell (FCPC) based cartilage gel through self-assembly for cartilage repair surgery, with clinically useful properties including adhesiveness, plasticity, and continued chondrogenic remodeling after transplantation. characterization of the gels according to in vitro self-assembly period resulted in increased chondrogenic features over time. Adhesion strength of the cartilage gels were significantly higher compared to alginate gel, with the 2-wk group showing a near 20-fold higher strength (1.8 ± 0.15 kPa vs. 0.09 ± 0.01 kPa, p < 0.001). The in vivo remodeling process analysis of the 2 wk cultured gels showed increased cartilage repair characteristics and stiffness over time, with higher integrationfailure stress compared to osteochondral autograft controls at 4 weeks (p < 0.01). In the nonhuman primate investigation, cartilage repair scores were significantly better in the gel group compared to defects alone after 24 weeks (p < 0.001). Cell distribution analysis at 24 weeks showed that human cells remained within the transplanted defects only. A self-assembled, FCPC-based cartilage gel showed chondrogenic repair potential as well as adhesive properties, beneficial for cartilage repair.

Development of Standardized Fetal Progenitor Cell Therapy for Cartilage Regenerative Medicine: Industrial Transposition and Preliminary Safety in Xenogeneic Transplantation

“…Preliminary safety had already been assessed during sub-cutaneous implantation of bioengineered constructs, yielding FE002-Cart hECPs in rodent and murine models, wherein no immune system activation or tumor formation had been noted [ 36 ]. Parallelly, Park et al have recently shown comparable results with hECPs isolated from a different anatomical site, a different cell culture initiation methodology, and a different preclinical model (i.e., non-human primate) [ 95 ]. With respect to the caprine model used for the present study, any efficacy demonstration was mitigated by the rates of delamination and subchondral bone cyst formation, caused by synovial fluid pressure increases, inducing the variability of results both in the CTRL and hECP groups.…”

From regeneration to osteoarthritis in the knee joint: The role shift of cartilage-derived progenitor cells

“…Recently, the combination of a couple of cellular differentiation (CD) markers were used for CPC identification. Interestingly, CD166 - cells showed no chondrogenic capacity ( Pretzel et al, 2011 ), but CD166 low/− CD73 + CD146 low/− LIN − CD44 low cells can only undergo chondrogenesis ( Wu et al, 2013 ).…”

Emerging Gene-Editing Modalities for Osteoarthritis

“…MSCs derived from fetal cells also have therapeutic properties, but ethical concerns have been raised about using them for treatment and therapeutic applications [ 78 , 79 ]. Additional challenges arise due to the potential of fetal MSCs to differentiate into several different types of cells, which might be more difficult to control and direct [ 76 , 80 , 81 ]. The capabilities of MSCs are usually age-dependent.…”