Overview of Cellular Therapeutics Clinical Trials: Advances, Challenges, and Future Directions

Abstract

Cellular therapeutics, encompassing stem cell-based regeneration and engineered immune cell platforms, have demonstrated efficacy in treating degenerative diseases, immune-related diseases, and oncology. However, low engraftment rates and limited long-term efficacy remain critical translational barriers. This review compiled clinical projects on cell therapy in China over the past five years (over 1200 patients across 172 clinical trials) to highlight its rapid development in recent years and illustrate the directions of indications for application. This review also analyzes published clinical achievements all over the world, revealing significant therapeutic improvements in degenerative disorders (40-60% improvement in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and oncology (78% ctDNA clearance, p < 0.001)). We propose integrating traditional Chinese medicine (TCM) bioactive compounds to enhance cell viability via C-X-C motif chemokine receptor (CXCR4) upregulation and mitochondrial biogenesis. Despite mechanistic insights, translational barriers include limited TCM validation (72% lacking single-cell omics) and regulatory misalignment. Future efforts should prioritize randomized trials and standardized TCM-cell therapy protocols to bridge discovery and clinical translation.

Keywords: CAR-T; MSC; cancer; cellular therapeutics; degeneration diseases; traditional Chinese medicine.

Figure 2

Recent clinical trials of stem cell therapies in China (classified by indication). There are 34 clinical trials for degenerative disorders, 14 related to immune-mediated diseases, and 9 for other complex illnesses.

Figure 3

Recent clinical trials of stem cell therapies in China (classified by cell type). The most common sources are UCMSCs (35 clinical trials), BMSCs (eight clinical trials), ADMSCs (five clinical trials), HSCs (four clinical trials), EMSCs and DPMSCs (two clinical trials each), AMSCs (one clinical trial), and PMSCs (one clinical trial).

Figure 1

Recent clinical trials of immune cell therapies in China (classified by cell type): CAR-T account for 96 clinical trials, T cells seven clinical trials, natural killer cells (NK) two clinical trials, tumor infiltrating lymphocytes (TIL) five clinical trials, dendritic cells (DC) three clinical trials, and chimeric antigen receptor- natural killer cells (CAR-NK) two clinical trials.

Figure 4

Potential mechanisms of MSC-based therapy for OA.

Figure 5

Generation of the neoTCR product for each patient.