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All Journal International Journal of Cell and Biomedical Science
Nugraha, Dendi Krisna
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Biochemistry, Genetics & Molecular Biology Immunology & microbiology Medicine & Pharmacology

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In Vitro Transcription as a Strategy to Enhance Mesenchymal Stem Cell Secretome for Therapeutic Use: An Overview Nugraha, Dendi Krisna; Falah, Ariq
International Journal of Cell and Biomedical Science Vol 3 No 9 (2024)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v3i9.61

Abstract

Mesenchymal stem cells (MSCs) have become a cornerstone of regenerative medicine owing to their capacity to secrete a diverse array of bioactive molecules, collectively termed the secretome. The MSC secretome exerts profound immunomodulatory, anti-inflammatory, and trophic effects that underpin much of the therapeutic efficacy observed in MSC-based interventions. Nevertheless, variability in the secretory profile across donors, tissue sources, and culture conditions continues to limit the reproducibility and potency of MSC-derived therapies. Recent advancements in in vitro transcription (IVT) mRNA technology have emerged as a robust and transient platform for the reprogramming of mesenchymal stem cells (MSCs) without the need for genomic integration. Through the use of IVT-mRNA-mediated expression of selected cytokines, growth factors, or homing receptors, MSCs can be endowed with enhanced anti-inflammatory and regenerative capabilities while preserving their native phenotype and viability. This review summarizes current IVT-mRNA–based strategies for engineering the MSC secretome, with an emphasis on augmenting anti-inflammatory cytokines (e.g., IL-10, TSG-6) and growth factors (e.g., VEGF, HGF, FGF2). The review also examines how IVT-mRNA redefines the cellular secretory landscape, outlines key considerations in IVT-mRNA design and optimization, and discusses translational implications for both cell-based and cell-free therapeutic applications. Finally, it underscores persistent challenges, including transient transgene expression, innate immune activation, and delivery inefficiency, and contemplates future prospects for integrating IVT-mRNA technology with advanced biomaterials, cellular priming methodologies, and multifactorial modulation to achieve consistent and potent therapeutic secretomes.
Human-Umbilical Cord-Mesenchymal Stem Cells (hUC-MCSs) Therapy with Extravesicles (EVs) Booster Improves Recovery in Type 2 Diabetes Mellitus with Cardiovascular Disease Nugraha, Dendi Krisna; Jutadi; Anggoro, Naufal Sebastian; Sari, Fikriya Novita; Ardani, Yanuar
International Journal of Cell and Biomedical Science Vol 4 No 10 (2025)
Publisher : Stem Cell and Cancer Research (SCCR)

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.59278/cbs.v4i10.66

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Background: Type 2 diabetes (T2DM) is a chronic metabolic disorder characterized by insulin resistance and β-cell dysfunction, leading to persistent hyperglycemia and complications. Studies have explored mesenchymal stem cell (MSC)-based therapies and their extracellular vesicles (EVs) as novel approaches for metabolic regulation and tissue repair. Case: A 43-year-old male patient exhibited symptoms including excessive thirst and hunger, frequent urination, fatigue, and intermittent blurry vision. He had type 2 diabetes and recently worsened symptoms. The obese patient had elevated blood glucose, HbA1c, triglycerides, and uric acid. He received umbilical cord-derived mesenchymal stem cells (161,6 × 106 cells), followed by seven intramuscular EV injections (1.5 cc each), along with diet and antioxidant supplements. Results: Three months after the conclusion of treatment, laboratory test showed significant improvement, with fasting glucose levels measuring at 91 mg/dL, HbA1c levels at 5,1%, triglyceride levels at 151 mg/dL, uric acid levels at 4,9 mg/dL, and an erythrocyte sedimentation rate of 12 mm/hr. The clinical symptoms such as nocturia, fatigue, and neuropathic pain, demonstrated a substantial improvement, as well as led to the resolution of skin xerosis and heel fissures. Conclusion: This case suggests that combined UC-MSC and EV therapy, complemented by lifestyle modification, may contribute to metabolic stabilization and symptomatic relief in T2DM patients.
Co-Authors Anggoro, Naufal Sebastian Ardani, Yanuar Falah, Ariq Jutadi Sari, Fikriya Novita