Cellular therapy for locomotor function: Translating potential into practice

Abstract

This editorial introduces a special issue on cell-based therapies for disorders affecting locomotor function. The articles span a range of approaches, including methods to enhance immunological compatibility in induced pluripotent stem cell transplantation, as well as clinical and preclinical investigations using mesenchymal stem cells for the treatment of osteoarthritis. These studies address different therapeutic strategies and stages of development, reflecting ongoing efforts to translate basic research into safe and practical treatments for locomotor conditions.

The restoration of motor function in locomotor disorders has long posed a shared challenge for both clinicians and researchers. In recent years, cell therapy has gained attention as a promising strategy within regenerative medicine, offering new therapeutic options for conditions that have been difficult to manage with conventional approaches. Motor function is primarily impaired by disorders of the brain, spinal cord, peripheral nerves, muscles, and joints. Particularly, central nervous system (CNS) disorders cause significant socioeconomic losses, prompting many researchers to challenge Cajal’s dogma and to conduct research on CNS regeneration using cell therapy^1–3, with some of these studies have progressed to practical clinical trials^4,5. Meanwhile, research on cell therapy for muscles and joints, which significantly impacts patients’ quality of life, is also progressing steadily^6–9, suggesting that the implementation of cell therapy for “locomotor function” is advancing broadly. This special issue of Cell Transplantation, entitled “Cellular Therapy for Locomotor Function,” features a series of studies exploring the use of stem cell–based therapies aimed at improving motor function.

One major issue in transplantation therapies involving cell engraftment is achieving immunological compatibility while maintaining cost-effectiveness and broad clinical applicability. To address this, Sunwoong et al. ¹⁰ investigated the use of human leukocyte antigen (HLA)-homozygous induced pluripotent stem cell (iPSC) lines to increase the proportion of patients who could benefit from iPSC-based therapies. Their population genetics analysis, which included data from various ethnic and geographic groups, indicated the need to establish an international HLA-matched iPSC bank. By identifying haplotypes that could be applicable to a wide patient population, the study offers a practical direction for expanding the clinical availability of iPSC-derived treatments.

In contrast, mesenchymal stem cells (MSCs) offer a different therapeutic approach, particularly in settings where tissue replacement is not necessary. Lee et al. ¹¹ conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the effects of intra-articular injection of bone marrow-derived MSCs (BM-MSCs) in patients with knee osteoarthritis (OA). Twenty-four patients received either BM-MSCs or saline and were observed for 12 months. The treatment group showed significant improvements in pain and physical function scores (WOMAC and KOOS), compared to the control group. Magnetic resonance imaging (MRI) T2 mapping revealed a slower progression of cartilage degeneration on the medial side of the joint, suggesting a mechanistic basis for the clinical findings. The treatment was well tolerated, with only transient adverse effects such as joint pain and swelling. No serious adverse events occurred. These results indicate that intra-articular injection of allogeneic BM-MSCs may represent a safe and feasible outpatient treatment for OA.

Fukuda et al. ¹² examined a different MSC source by evaluating a human adipose-derived mesenchymal stem cell line (ASCL) in a rat model of OA induced by low-dose monoiodoacetic acid. Intra-articular administration of ASCLs resulted in reduced synovial inflammation, improved modified Mankin scores, decreased serum and synovial interleukin (IL)-6 levels, elevated pain thresholds, and better gait function. ASCLs have already been used in clinical settings for platelet production and represent a standardized, readily available cell product that avoids both donor-related variability and the need for invasive harvesting procedures. This study is the first to evaluate ASCLs in OA, demonstrating their potential applicability to multiple diseases.

Together, these three studies address different stages of the research and development pathway, ranging from cell sourcing strategies to preclinical and clinical investigations. Interestingly, all three studies employed allogeneic cells. Cell transplantation therapies may be broadly categorized by their intended function: (1) therapies based on the secretion of biologically active factors, such as cytokines; (2) therapies using cells with a transient lifespan but specific activity, such as T-lymphocytes; and (3) therapies that depend on stable engraftment and long-term function of the transplanted cells. The second and third categories raise concerns related to immunogenicity. In this issue, the study by Sunwoong et al. addresses this aspect directly. By contrast, the studies by Lee et al. and Fukuda et al. employed MSCs primarily for their paracrine effects, particularly anti-inflammatory actions, and thus paid less attention to immunogenicity. These differences reflect how the key technical challenges differ depending on the intended mechanism of action.

All three papers focus on applications that are close to clinical practice, reflecting the growing level of development in the field. It is also worth noting that the cell products used in the studies by Lee et al. and Fukuda et al. were supplied by commercial entities, suggesting increasing industrial involvement in cell-based therapies. We hope this special issue will provide useful insights for researchers working in this area and contribute to the further development of effective therapies for locomotor disorders.