With the advancement of regenerative medicine technologies, stem cell therapy has undergone more than a decade of rigorous safety and efficacy testing in the treatment of cartilage defects and for promoting cartilage regeneration.

Stem cells, as seed cells with multiple differentiation potentials, have recently demonstrated their advantages in treating cartilage lesions associated with osteoarthritis. Beyond their differentiation capabilities, stem cells can also secrete a variety of enzymes and trophic factors that participate in paracrine signaling—such as growth factors, cytokines, and chemokines—exerting protective effects against apoptosis, fibrosis, oxidative stress, and inflammation, while simultaneously promoting angiogenesis. Stem cell therapy effectively treats osteoarthritis through two distinct mechanisms:

1. Stem cells directly repair damaged tissues through their multidirectional differentiation potential. Under specific in vitro or in vivo induction conditions, stem cells can be transformed into osteoblasts and chondrocytes, enabling the regeneration of bone and articular cartilage.

2. Stem cells induce their own differentiation into chondrocytes by secreting various factors, such as transforming growth factor-β1 and insulin-like growth factor-1, while also inhibiting local inflammation progression and enhancing the natural repair capabilities of damaged tissues in the area—thereby achieving the desired therapeutic intervention.

Because human osteoarthritis develops relatively slowly—typically over about 30 years—it creates a favorable environment for stem cell applications. A growing body of ongoing and completed clinical study data suggests that stem cell therapy can effectively alleviate patients' pain, improve joint function, and enhance their overall quality of life.

In 2009, ChondroCelect, a product developed by Belgium's TiGenix (an autologous cartilage-derived cell therapy), was approved for use in repairing knee cartilage damage. In 2012, Cartistem, a stem-cell therapy from South Korea whose main ingredient is umbilical cord blood-derived mesenchymal stem cells, received approval for treating degenerative arthritis and repairing damaged knee cartilage. In October 2017, the *American Journal of Sports Medicine* published an article by Korean researchers including Chris Hyunchul Jo. The study found that, over a two-year follow-up period, intra-articular injections of autologous adipose tissue–derived mesenchymal stem cells were both safe and effective in treating knee osteoarthritis.

In April 2019, Chilean researchers Francisco Espinoza and colleagues published a phase I/II randomized, controlled clinical trial on stem cell therapy for knee osteoarthritis in *Stem Cell Translational Medicine* (NCT02580695). The trial findings revealed that multiple-dose stem cell treatment yielded superior outcomes compared to a single dose or hyaluronic acid (HA) supplementation.

The journal *Stem Cell Translational Medicine* has published the latest clinical trial data. Twelve patients aged 45 to 65, who suffered from moderate to severe knee osteoarthritis, underwent clinical treatment with stem cell therapy. After 12 months of follow-up, all participants showed significant improvements in both pain levels and quality of life. The study also demonstrated that stem cell therapy is safe, with higher doses correlating with more pronounced therapeutic effects.

The U.S. FDA has approved an Investigational New Drug (IND) application for a stem cell therapy targeting osteoarthritis. The treatment uses fat-derived stem cells and was developed by the U.S.-based stem cell company, Personalized Stem Cells. The company has now initiated the first clinical study focused on knee osteoarthritis.

Currently, several domestic clinical research projects focusing on stem cell therapy for osteoarthritis have completed their registration in accordance with the "Administrative Measures for Clinical Research on Stem Cells (Trial)" (Guowei Kejiaofa [2015] No. 48). In February 2019, CCTV.com—[Hunan News Broadcast] reported that osteoarthritis can be effectively managed through stem cell intervention, and several domestic projects have already been approved to advance into clinical research and eventual translational application stages.

Earlier, the article "15 Clinically Supported Evidence: Mesenchymal Stem Cell Therapy for Knee Osteoarthritis Cartilage Injury Is Safe and Effective" compiled data from 15 human clinical trials evaluating mesenchymal stem cell treatment for osteoarthritis. These findings not only highlight the efficacy and safety of MSC intervention in addressing osteoarthritis but also suggest that, in some cases, MSC-based treatment approaches come closer to achieving desired outcomes compared to conventional therapies.

As shown in the image, cartilage gradually heals over time, moving from left to right.

As shown in the figure, both the low-dose and high-dose groups experienced a decrease in VAS scores (a pain indicator).

Before treatment (left), most of the cartilage is yellow; after treatment (right), blue clearly predominates, indicating an improvement in cartilage quality.

The image above shows an MRI comparison before and after treatment. As before, the bluer the color, the better the cartilage quality. Clearly, cartilage quality has improved significantly following the treatment.

Figure A shows the arthroscopic findings before treatment, revealing cartilage defects. Figure B illustrates the treatment combining adipose-derived mesenchymal stem cells with PRP, while Figure C presents the post-treatment results, demonstrating successful cartilage repair.