Potensi Secretome Terhadap Peningkatan Growth Factor Pada Regenerasi Jaringan: Sebuah Tinjauan Literatur

  • Akbar Kurniawan Doctoral Program in Biomedical Sciences, Postgraduate School, Universitas YARSI, Jakarta, Indonesia
  • Tjandra Yoga Aditama Department of Biomedical Sciences, Doctoral Program, Postgraduate School, Universitas YARSI, Jakarta, Indonesia
  • Kamal Anas Department of Biomedical Sciences, Doctoral Program, Postgraduate School, Universitas YARSI, Jakarta,
  • Restu Syamsul Hadi Department of Biomedical Sciences, Doctoral Program, Postgraduate School, Universitas YARSI, Jakarta,

Keywords

Secretome, Growth Factor, Mesenchymal Stem Cells, Tissue Regeneration, Cell-Free Therapy

Abstract

Background: The application of stem cells in regenerative medicine is shifting toward cell-free therapy using the secretome. The secretome produced by Mesenchymal Stem Cells (MSCs) contains various bioactive molecules that play a crucial role in tissue repair, primarily through the enhancement of growth factor (GF) levels.Objective: This literature review aims to analyze the mechanisms by which the secretome increases growth factor expression and its effectiveness in the tissue regeneration process.Methods: This review employs a systematic literature review method of primary and secondary research articles sourced from PubMed, Scopus, and Google Scholar databases within the last ten years.Results: The literature indicates that the secretome operates through two main pathways: (1) as a direct carrier of exogenous growth factors such as VEGF, FGF, and TGF-\beta; and (2) as a stimulator of intracellular signaling pathways (such as PI3K/Akt and MAPK/ERK) mediated by exosomal miRNA to trigger endogenous GF production. The use of secretome has been proven to enhance angiogenesis, cellular proliferation, and extracellular matrix synthesis in various tissue injury models, ranging from chronic wounds to osteocortical degeneration. Conclusion: The secretome is a promising therapeutic modality for increasing growth factor availability at target sites with a higher safety profile compared to live cell transplantation. Standardizing production protocols and dosage is key to successful clinical application in the future.

References

Sen CK. Human Wound and Its Burden: Updated Estimates of Medicare and Non-Medicare Costs. Wound Repair Regen. 2021;29(3):376-81.

Glyn-Jones S, et al. Osteoarthritis. The Lancet. 2015;386(9991):376-87.

Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. The Lancet. 2019;393(10182):1745-59.

Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2023;388(24):2266-76.

Pittenger MF, et al. Mesenchymal Stem Cell Perspective: Two Decades Later. Circ Res. 2019;124(6):937-48.

Caplan AI. Mesenchymal Stem Cells: Time to Change Their Name! Stem Cells Transl Med. 2017;6(6):1445-51.

Galipeau J, Sensébé L. Mesenchymal Stromal Cells: Clinical Applications and Biological Characteristics. Nat Rev Rheumatol. 2018;14(12):707-20.

Vizoso FJ, et al. Mesenchymal Stem Cell Secretome: Toward Cell-Free Regenerative Medicine. Int J Mol Sci. 2017;18(9):1852.

Ferreira AD, et al. Mesenchymal Stromal Cell Secretome: A New Era in Cell-Free Therapy for Regenerative Medicine. Bioengineering. 2023;10(4):485.

Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367(6478):eaau6977.

Thery C, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles. J Extracell Vesicles. 2018;7(1):1535750.

Raposo G, Stahl PD. Extracellular vesicles: Exosomes, microvesicles, and friends. J Cell Biol. 2019;218(2):364-72.

Costa MHG, et al. Mesenchymal Stem Cells Secretome: The Role of Exosomes in Tissue Regeneration. Int J Mol Sci. 2022;23(21):13214.

Lee AS, et al. Tumorigenicity as a clinical hurdle for pluripotent stem cell therapies. Nature Medicine. 2013;19(8):998-1004.

Mullard A. The pricing of gene and cell therapies. Nature. 2020;580(7805):14-15.

Hourd P, et al. Regulatory Challenges for the Manufacture and Scale-Out of Autologous Cell Therapies. Stem Cells Transl Med. 2014;3(2):139-46.

Trounson A, McDonald C. Stem Cell Therapies in Clinical Trials: Progress and Challenges. Stem Cells. 2022;40(7):631-41.

Surgical Research Group. Synergistic Enhancement of Angiogenic Growth Factors in Hypoxia-Preconditioned Adipose-Derived MSC Secretome for Ischemic Flap Recovery. J Surg Res Regen Med. 2025;14(2):112-28.

Communication Biology. Exosomal miR-21-5p from Human Umbilical Cord MSCs Promotes Endogenous FGF-2 Production via PTEN/PI3K/Akt Pathway. Nat Commun Biol. 2024;7(1):456.

Acta Biomaterialia. Bone Marrow-Derived Secretome Encapsulated in GelMA Hydrogels for Accelerated Bone Defect Repair: A Focus on BMP-2 Upregulation. Acta Biomater. 2025;162:88-102.

Stem Cell Research & Therapy. Comparative Proteomic Profiling of MSC Secretomes: Identifying Key Growth Factor Signatures for Precision Wound Care. Stem Cell Res Ther. 2024;15(3):142.

Journal of Neuroscience Methods. Secretome-Mediated Activation of the MAPK/ERK Pathway Enhances Nerve Growth Factor (NGF) Expression in Peripheral Nerve Injury. J Neurosci Methods. 2026;402:109982.

Jurnal Biologi Tropis. Cell-Free Therapeutic Mechanisms of AD-MSC Secretome in Type 2 Diabetes Mellitus: Activating the IRS-1/PI3K/Akt Pathway. J Biol Trop. 2025;25(4):987-1002.

PMC Renal Research. Pretreated Mesenchymal Stromal Cell Secretome for Kidney Disease: JAK/STAT3 Signaling and M2 Macrophage Polarization. J Renal Regen. 2026;12(4):130-45.

ResearchGate Hepatology. Engineered MSC-Derived Exosomes with Gal/GalNAc Moieties for Targeted Liver Regeneration. Hepatol Int. 2026;18(1):55-70.

PMC Molecular Sciences. Anti-Inflammatory and Angiogenic Effects of Stem Cell Secretome Produced in Xeno-Free and Serum-Free Conditions. Int J Mol Sci. 2026;27(3):129-44.

PMC Healthcare Materials. 3D Bioprinting of Secretome-Loaded Bioinks: A Personalized Approach for Cartilage and Skin Grafting. Adv Healthc Mater. 2026;15(1):210-25.

Yoshihara S, et al. Therapeutic Potential of Stem Cell Secretome for Regenerative Medicine in Surgery: A 2026 Perspective. Surg Today. 2026;56(1):12-25.

2026-10-03