Stem cell-based cartilage regeneration: Biological strategies, engineering innovations, and clinical translation

Table 1 Summary of stem cell therapies for cartilage regeneration

Stem cell type	Advantages	Challenges	Clinical stage	Ref.
Bone marrow-derived MSCs	Well-studied; strong chondrogenic potential	Painful harvest; limited yield in elderly	Phase I/II trials	Wakitani et al[40], 2004
Adipose-derived MSCs	High yield; minimally invasive harvest	Variable quality; less matrix production than BMSCs	Phase I/II trials	Lee et al[20], 2019
Infrapatellar fat pad MSCs	Joint-derived; OA-primed immunomodulatory phenotype	Limited standardization; less explored	Early clinical research	Koh and Choi[101], 2012
Synovium-derived MSCs	High chondrogenic capacity; joint niche origin	Harvest from inflamed OA synovium; invasive	Preclinical to early clinical	Jeyaraman et al[102], 2022
Induced pluripotent stem cells	Unlimited expansion; autologous potential	Tumorigenicity risk; ethical and regulatory hurdles	Preclinical	Yamashita et al[47], 2015
Nasal chondrocytes	Phenotypic stability; easy to harvest	Non-joint origin; limited studies	Phase I	Mumme et al[48], 2016

MSCs: Mesenchymal stem cells; BMSCs: Bone marrow-derived mesenchymal stem cells; OA: Osteoarthritis.

Table 2 Animal models for preclinical cartilage regeneration

Species	Cartilage thickness	Advantages	Limitations
Mouse	20-30 μm	Low cost, genetic models available	Extremely thin cartilage, not load-bearing
Rat	100-150 μm	Inexpensive, widely used, easy handling	Thin cartilage, less similar to humans
Rabbit	200-300 μm	Moderate size, suitable for defect modeling	Rapid healing not reflective of humans
Goat	1000-2000 μm	Load-bearing joints, similar cartilage size	Higher cost, ethical concerns
Pig	900-1300 μm	Joint size, cartilage thickness similar to humans	Expensive, difficult handling
Sheep	700-1200 μm	Weight-bearing joints, suitable for long-term studies	Expensive, anatomical differences