Abstract
Infrapatellar fat pad–derived mesenchymal stem cells (IPFP-MSCs) are a type of adipose-derived stem cell (ADSC). They potentially contribute to cartilage regeneration and modulation of the immune microenvironment in patients with osteoarthritis (OA). The ability of IPFP-MSCs to increase chondrogenic capacity has been reported to be greater, less age dependent, and less affected by inflammatory changes than that of other MSCs. Transcription-regulatory factors strictly regulate the cartilage differentiation of MSCs. However, few studies have explored the effect of transcriptional factors on IPFP-MSC-based neocartilage formation, cartilage engineering, and tissue functionality during and after chondrogenesis. Instead of intact MSCs, MSC-derived extracellular vesicles could be used for the treatment of OA. Furthermore, exosomes are increasingly being considered the principal therapeutic agent in MSC secretions that is responsible for the regenerative and immunomodulatory functions of MSCs in cartilage repair. The present study provides an overview of advancements in enhancement strategies for IPFP-MSC chondrogenic differentiation, including the effects of transcriptional factors, the modulation of released exosomes, delivery mechanisms for MSCs, and ethical and regulatory points concerning the development of MSC products. This review will contribute to the understanding of the IPFP-MSC chondrogenic differentiation process and enable the improvement of IPFP-MSC-based cartilage tissue engineering.
Highlights
Introduction iationsOsteoarthritis (OA) is the most common degenerative joint disease and is characterized by progressive articular-cartilage loss
RUNX2 and myocyte enhancer factor-2C (MEF2C) have been implicated as key transcription factors regulating chondrocyte hypertrophy, as they drive the expression of terminal differentiation markers, type X collagen, MMP3, matrix metalloproteinase 13 (MMP13), integrin-binding sialoprotein (IBSP), Indian hedgehog (Ihh), and alkaline phosphatase [38]
The negative regulators Slug and C/EBPβ are expressed by hypertrophic chondrocytes, which indicates that they control terminal chondrocyte differentiation and promote endochondral ossification [58] (Figure 2). δEF1, AP-2α, and Twist1 are expressed by chondrocyte progenitors and prevent the production of cartilage-like mesenchymal tissue, indicating that they negatively regulate early phase chondrogenesis [59–63]
Summary
Figure infrapatellar fatfat pad–derived mesenchymal stem cells (IPFP-MSCs) and and subcutaneous subcutaneous ADSCs. Patient age is a crucial parameter that sometimes limits the success of cell therapy. Patient age is a crucial parameter that sometimes limits the success of cell therapy Unlike those of BMSCs, the proliferation and differentiation capacities of infrapatellar. Pad–derived MSCs (IPFP-MSCs) do not differ significantly among patient age groups. This makes them promising for use in stem-cell-based regenerative therapy [6]. MSCs at late passages exhibit senescent phenotypes with reduced proliferative caity and suboptimal multidifferentiation potential [7]. The potential of MSC-derived-exosome cell-freeregeneration therapy for OA treatment is discussed. The potential of MSC-derived-exosome cell-free therapy for OA treatment is discussed
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