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“Clinical Utility of Mesenchymal Stem/Stromal Cells in Regenerative Medicine and Cellular Therapy” by Maldonado et al., Journal of Biological Engineering (2023) Clinical Utility of MSC Stem Cell in Regenerative Medicine

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1. Overview of MSC Stem Cell

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic stem cells capable of self-renewal, multilineage differentiation, and strong immunomodulation. They can be derived from multiple sources such as bone marrow, adipose tissue, umbilical cord, placenta, amniotic fluid, cord blood, and dental pulp. Their ease of isolation, low immunogenicity, and paracrine signaling activity make them key candidates in regenerative and cellular therapy.

The International Society for Cellular Therapy (ISCT) defines MSC stem cells by adherence to plastic under standard culture, fibroblast-like morphology, differentiation into osteoblasts, adipocytes, and chondrocytes, and surface antigen expression (CD73⁺, CD90⁺, CD105⁺; negative for CD45, CD34, CD14, CD19, HLA-DR).

MSC stem cells exert therapeutic effects mainly through paracrine secretion of trophic, immunomodulatory, and anti-inflammatory factors, promoting angiogenesis, anti-fibrosis, neurogenesis, and tissue repair.

2. Source-Specific Characteristics

Different tissue origins impart unique biological properties:

Source

Advantages

Distinct Markers / Notes

Bone Marrow (BM-MSCs)

Gold standard; high differentiation potential

Painful extraction; limited yield

Adipose (Ad-MSCs)

Easily accessible, abundant

Express CD36, CD200, CD274; need higher growth factor doses for chondrogenesis

Placenta (P-MSCs)

Abundant and immunoprivileged

Express UEA-1, CD166, CD44; heterogeneous proliferation rates

Amniotic Fluid (AF-MSCs)

Rapid proliferation; hepatic differentiation

Stable karyotype, high self-renewal

Umbilical Cord (UC-MSCs)

Non-invasive collection; high proliferation

Similar to BM-MSCs, but better expansion and lower immunogenicity

Cord Blood (UCB-MSCs)

Low CD105/CD90; limited adipogenesis

Long culture lifespan

Dental Pulp (DP-MSCs)

High growth factor expression, neural crest origin

High odontogenic differentiation capacity

3. Therapeutic Applications

MSC stem cells are being studied in more than 1,400 clinical trials globally across musculoskeletal, nervous, cardiovascular, and immune systems, demonstrating their versatility in regenerative medicine.

A. Musculoskeletal Disorders

• Muscular Dystrophy: UC-MSC stem cells and placental MSC stem cells improved muscle strength, reduced fibrosis and inflammation, and increased utrophin expression.
• Osteonecrosis: BM-MSC stem cells enhanced bone repair and angiogenesis in steroid-induced necrosis. Exosome-mediated osteogenesis was observed via SOX9 upregulation.
• Cranial Defects: BM-MSC stem cells, UC-MSC stem cells, and DP-MSCs all promoted bone regeneration, osteocalcin expression, and angiogenesis.
• Non-Union Bone Fractures: Ad-MSC stem cells, UC-MSCstem cells, and BM-MSC stem cells accelerated bone union and vascularization.
• Osteoarthritis: Intra-articular MSC injections improved pain, mobility, and cartilage volume, with higher doses showing better outcomes.

B. Nervous System Disorders

• Alzheimer’s Disease: MSC-derived exosomes reduced β-amyloid plaques, induced neurogenesis, and decreased neuroinflammation through molecular signaling pathways such as Wnt/β-catenin.
• Parkinson’s Disease: UC-MSC stem cells protected dopaminergic neurons, restored BDNF and NGF, and improved motor function.
• Multiple System Atrophy: BM-MSC stem cells and Ad-MSC stem cells slowed disease progression and neurodegeneration.
• ALS (Amyotrophic Lateral Sclerosis): MSC stem cellsimproved survival, decreased inflammatory cytokines, and enhanced neurotrophic factor release.
• Spinal Cord Injury: UC-MSC stem cells and Ad-MSCstem cells improved motor and sensory recovery through neural regeneration and nerve growth factor secretion.

C. Cardiovascular Diseases

• Hypertension: MSC-derived exosomes reduced arterial stiffness, improved endothelial nitric oxide synthase activity, and restored normal cardiac function.
• Myocardial Infarction: Exosomes from Ad-MSCs and UC-MSCs promoted angiogenesis, decreased fibrosis, and improved cardiac performance.
• Stroke: BM-MSC exosomes reduced infarct size, increased angiogenesis, and improved neurological recovery through microRNA signaling.
• Heart Failure: UC-MSC stem cells, BM-MSC stem cells, and Ad-MSC stem cells improved cardiac ejection fraction, reduced fibrosis, and enhanced contractility.

D. Immune-Related Disorders

MSC stem cells modulate both innate and adaptive immunity, inhibiting T-cell proliferation and promoting regulatory T cells (Tregs). They shift macrophages from a pro-inflammatory (M1) to a healing (M2) phenotype, resolving inflammation.

• Type 1 Diabetes Mellitus: MSC stem cells lowered blood glucose and promoted pancreatic repair.
• Rheumatoid Arthritis: UC-MSC stem cells reduced IL-6, increased IL-10, and improved joint function.
• Systemic Lupus Erythematosus: UC-MSC stem cellsdecreased disease activity and improved renal function.
• Graft-Versus-Host Disease: MSC stem cells improved survival rates and remission outcomes through immune regulation.

4. Emerging Trends: Exosomes and Genetic Enhancement

MSC-derived exosomes replicate the benefits of MSC stem cellswhile minimizing transplantation risks. These extracellular vesicles carry proteins, mRNA, and microRNAs that influence tissue regeneration and immune balance.
Genetic modification of MSC stem cells to express neuroprotective or anti-inflammatory molecules — such as TIMP2, adrenomedullin, or anti-miR-155 — enhances therapeutic performance.

5. Conclusion

Mesenchymal stem/stromal cells show broad clinical potential across musculoskeletal, neurological, cardiovascular, and immune-related diseases. Their regenerative, immunoregulatory, and paracrine mechanisms enable both tissue repair and immune modulation.

Among the different cell sources, umbilical cord MSC stem cells stand out for scalability, safety, and potency, while exosome-based therapy represents the next generation of regenerative medicine — offering safe, cell-free, and clinically adaptable solutions.