Novel isolation technology with convincing evidence in secretome clinical application: A Case Report

Main Article Content

Fu Nan Wang, MD, PhD Sebo Gene Wang Ming Chu Hsu Sebo Ling Wang Sebo Dih Wang James J. Huang

Abstract

A novel and natural mesenchymal stem cell isolation procedure without the incorporation of any chemical or biological agents from fresh umbilical cord through cultural expansion and harvest is described, the resulting cells can be maintained up to 20 passages and exhibited MSC morphology and characteristics. Proficient and straight forward secretome complex was harvested from these stem cell cultures after cells reached genetic stability. The process was straightforward, sustainable and scalable; the secretome complex depicted reproducible clinical end-point evident disease-modifying activity in various clinical applications. These stem cell isolation processes exemplified a proficient and sustainable cell expansion protocol and the harvested secretome component that depicted clinical efficacy warrants further investigation.

Keywords: Mesenchymal stem cells, umbilical cord–derived stem cells, secretome, stem cell isolation, cell-free therapy, regenerative medicine

Article Details

How to Cite
WANG, Fu Nan et al. Novel isolation technology with convincing evidence in secretome clinical application: A Case Report. Medical Research Archives, [S.l.], v. 13, n. 8, aug. 2025. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/6750>. Date accessed: 18 feb. 2026. doi: https://doi.org/10.18103/mra.v13i8.6750.
Section
Research Articles

References

1. Dixit P, Katare P. Challenges in identifying the best source of stem cells for cardiac regeneration therapy. Stem Cell Research & Therapy. 2015; 6:26. DOI: 10.1186/s13287-015-0010-8

2. Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry. 2018; 93 (1):19-31. doi: 10.1002/cyto.a.23242.

3. Ikehara, S. Grand challenges in stem cell treatments. Front Cell Dev Biol. 2013; 1: 2. doi:10. 3389/fcell.2013.00002,

4. Mitrano TI, Grob MS, Carri F, Nova-Lamperti E, Luz PA, Fierro FS, Quintero A, Chaparro A, Sanz A. Culture and characterization of mesenchymal stem cells from human gingival tissue. J Periodontol. 2010; 81(6):917–925 DOI:10.1902/jop.2010.090566

5. Sotiropoulou PA, Perez SA, Salagianni M, Baxevanis CN, Papamichail M. Characterization of the Optimal Culture Conditions for Clinical Scale Production of Human Mesenchymal Stem Cells. Stem Cells, 2006;24 (2):462–471. doi.org/10.1634/ stemcells.2004-0331

6. Akbar A, Malekian F, Baghban N, Kodam SP, Ullah M. Methodologies to Isolate and Purify Clinical Grade Extracellular Vesicles for Medical Applications. Cells. 2022;11(2):186. doi: 10.3390/ cells11020186

7. Ståhl A, Johansson K, Mossberg M, Kahn R, Karpman D. Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases. Pediatr Nephrol. 2017; 34(1):11–30. doi: 10.1007/ s00467-017-3816-z

8. Kwon HH, Yang SH, Lee J, Park BC, Park KY, Jung JY, Bae Y, Park G. Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study. Acta Derm Venereol. 2020;100 (18):adv00310. Doi: 10.2340/00015555-3666.

9. Keller A, Claudia Spits C. The Impact of Acquired Genetic Abnormalities on the Clinical Translation of Human Pluripotent Stem Cells. Cells. 2021; 10(11):3246. doi: 10.3390/cells10113246

10. Wyles SP, Brandt EB, Nelson TJ. Stem Cells: The Pursuit of Genomic Stability. Int J Mol Sci. 2014 ;15(11):20948–20967. doi: 10.3390/ijms151120948

11. Mas-Bargues C, Sanz-Ros J, Román-Domínguez A, Inglés M, Gimeno-Mallench L, Alami ME, Viña-Almunia J, Gambini J, Viña J, Borrás C. Relevance of Oxygen Concentration in Stem Cell Culture for Regenerative Medicine. Int J Mol Sci. 2019;20(5):1195. doi: 10.3390/ijms20051195

12. Viggiano L, Marsano RM. The Stability and Evolution of Genes and Genomes. Genes. 2023; 14(9):1747. doi: 10.3390/genes14091747

13. Katia Mareschi K, Niclot AGSB, Marini E, Bari E, Labanca L, Lucania G, Ferrero E, Perteghella S, Torre ML, Franca Fagioli F. A New Human Platelet Lysate for Mesenchymal Stem Cell Production Compliant with Good Manufacturing Practice Conditions Preserves the Chemical Characteristics and Biological Activity of Lyo-Secretome Isolated by Ultrafiltration. Int J Mol Sci. 2022;23(8):4318. doi: 10.3390/ijms23084318.

14. Hassan G,, Kasem I, Soukkarieh C, Aljamali M. A Simple Method to Isolate and Expand Human Umbilical Cord Derived Mesenchymal Stem Cells: Using Explant Method and Umbilical Cord Blood Serum. Int J Stem Cells. 2017;10(2):184–192. doi: 10.15283/ijsc17028

15. Hassan G, Kasem I, Antaki R, Mohammad MB , AlKadry R, Aljamali M. Isolation of umbilical cord mesenchymal stem cells using human blood derivatives accompanied with explant method. Stem Cell Investig. 2019; 6:28. doi: 10.21037/ sci.2019.08.06

16. Han Y, Tao R, Sun T, Chai J, Xu G, Jing Liu J. Optimization of human umbilical cord mesenchymal stem cell isolation and culture methods. Cytotechnology. 2013;65(5):819–827. doi: 10.1007/s10616-012-9528-0

17. Takahashi K, and Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2016; 126(4): 663-676 doi: 10.1016/j.cell.2006.07.024.

18. Rippon HJ, and Bishop AE. Embryonic stem cells”, 2004; Cell Prolif. 37(1):22-23. DOI: 10.1111/ j.1365-2184.2004.00298.x

19. Knoepfler PS., Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells.2009; 27 (5): 1050–1056. DOI: 10.1002/stem.37

20. Wang SG, Hsu, NC, Wang, SM, and Wang, FN. Successful Treatment of Plaque Psoriasis with Allogeneic Gingival Mesenchymal Stem Cells: A Case Study. Dermatol Medicine 2020: 1- 4. DOI: 10.1155/2020/4617520

21. Wang SG, Hsu, NC, Wang, SM, Hsu, MC and Wang, FN. First-in- human High Cumulative Dose Mesenchymal Stem Cell Therapy in Multiple Myelomas: A Case Report. J. Hematol. and Transfu 2021;8(1):1090 -1093

22. Wang FN, Hsu MC, Wang SL, Wang SG, Chen WC, Lee TD, Wang SM, and Doong H. Stem cell therapy: A Possibility for Coronavirus. J. Hematol and Transfus. 2021;8 (2):1094-1096

23. Wang SG, Wang SM, Hsu MC, Wang FN. Mesenchymal stem cell treatment improves renal failure and multiple episodes of nephrolithiasis. Journal of Urology and Research.2022; 91(1):1130 – 1132

24. Wang, FN., Ed, American Stem Cell Medicine Ace Review. Book Series of The World Medical Health Organization of The United Nations. American Stem Cell Base, Publisher, United States, 2024; ISBN 979-8-218-97499-2

25. Neri S. Genetic Stability of Mesenchymal Stromal Cells for Regenerative Medicine Applications: A Fundamental Biosafety Aspect. Int J Mol Sci. 2019;20(10):2406. doi: 10.3390/ijms20102406

26. Trzyna A, Banaś-Ząbczyk A. Adipose-Derived Stem Cells Secretome and Its Potential Application in "Stem Cell-Free Therapy". Biomolecules. 2021; 11(6):878 doi: 10.3390/biom11060878.