The Effect of Mesenchymal Stem Cells Derived-Conditioned Media in Combination with Oral Anti-Androgenic Drugs on Male Pattern Baldness: An Animal Study

Document Type : Original Article


1 Department of Tissue Engineering and Applied Cell Sciences, School of Advance Medical Science and Technology, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

3 Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

5 Department of Tissue Engineering and applied cell science, School of Advanced Medical Sciences & Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

6 Department of Biology, Faculty of Science, Razi University, Kermanshah, Iran

7 Department of Biology, Zand Institute of Higher Education, Shiraz, Iran

8 Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

9 Department of Tissue Engineering and Cell Therapy, School of Advanced Technologies in Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

10 Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

11 Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran


Objective: Androgenetic alopecia (AGA) is a prevalent form of hair loss, mainly caused by follicular sensitivity to
androgens. Despite developing different anti-androgen treatment options, the success rate of these treatments has
been limited. Using animal models, this study evaluated the therapeutic effects of umbilical cord (UC) stem cell
conditioned media (CM) combined with oral anti-androgens for hair regeneration.
Materials and Methods: In this experimental study, Poloxamer 407 (P407) was used as a drug carrier for
subcutaneous testosterone injection. AGA models were treated with oral finasteride, oral flutamide, and CM
injections. Samples were thoroughly evaluated and compared using histological, stereological, and molecular
Results: Injecting CM-loaded hydrogel alone or combined with oral intake of anti-androgens improved hair regeneration.
These treatments could promote hair growth by inducing hair follicles in the anagen stage and shortening the telogen
and catagen phases. Furthermore, the combination treatment led to an upregulation of hair induction gene expression
with a downregulation of inflammation genes.
Conclusion: Through a reduction in inflammation, injection of CM-loaded hydrogel alone or combined with oral intake
of anti-androgens induces the hair cell cycle with regeneration in damaged follicles. Hence, this could be a promising
therapeutic method for AGA patients.


Main Subjects

  1. Devjani S, Ezemma O, Kelley KJ, Stratton E, Senna M. Androgenetic alopecia: therapy update. Drugs. 2023; 83(8): 701-715.
  2. Ho CH, Sood T, Zito PM. Androgenetic alopecia. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: (16Oct 2022).
  3. Lolli F, Pallotti F, Rossi A, Fortuna MC, Caro G, Lenzi A, et al. Androgenetic alopecia: a review. Endocrine. 2017; 57(1): 9-17.
  4. Anastassakis K. Flutamide. Androgenetic alopecia from A to Z. Springer; 2022; 193-197.
  5. Saceda-Corralo D, Domínguez-Santas M, Vañó-Galván S, Grimalt R. What’s new in therapy for male androgenetic alopecia? Am J Clin Dermatol. 2023; 24(1): 15-24.
  6. Allam S, Elsakka EGE, Ismail A, Doghish AS, Yehia AM, Elkady MA, et al. Androgen receptor blockade by flutamide down-regulates renal fibrosis, inflammation, and apoptosis pathways in male rats. Life Sci. 2023; 323: 121697.
  7. Lei M, Yang L, Chuong CM. Getting to the core of the dermal papilla. J Invest Dermatol. 2017; 137(11): 2250-2253.
  8. Rahmani W, Abbasi S, Hagner A, Raharjo E, Kumar R, Hotta A, et al. Hair follicle dermal stem cells regenerate the dermal sheath, repopulate the dermal papilla, and modulate hair type. Dev Cell. 2014; 31(5): 543-558.
  9. Mohammadi P, Youssef KK, Abbasalizadeh S, Baharvand H, Aghdami N. Human hair reconstruction: close, but yet so far. Stem Cells Dev. 2016; 25(23): 1767-1779.
  10. Krefft-Trzciniecka K, Piętowska Z, Nowicka D, Szepietowski JC. Human stem cell use in androgenetic alopecia: a systematic review. Cells. 2023; 12(6): 951.
  11. Tabatabaei Qomi R, Sheykhhasan M. Adipose-derived stromal cell in regenerative medicine: a review. World J Stem Cells. 2017; 9(8): 107-117.
  12. Giuliano E, Paolino D, Fresta M, Cosco D. Drug-loaded biocompatible nanocarriers embedded in poloxamer 407 hydrogels as therapeutic formulations. Medicines (Basel). 2018; 6(1): 7.
  13. Kamishima T, Hirabe C, Ohnishi T, Taguchi J, Myint KZY, Koga S. Trichoscopic evaluation of dental pulp stem cell conditioned media for androgenic alopecia. J Cosmet Dermatol. 2023; 22(11): 3107- 3117.
  14. Yuan A, Gu Y, Bian Q, Wang R, Xu Y, Ma X, et al. Conditioned media-integrated microneedles for hair regeneration through perifollicular angiogenesis. J Control Release. 2022; 350: 204-214.
  15. Asadi-Golshan R, Razban V, Mirzaei E, Rahmanian A, Khajeh S, Mostafavi-Pour Z, et al. Efficacy of dental pulp-derived stem cells conditioned medium loaded in collagen hydrogel in spinal cord injury in rats: Stereological evidence. J Chem Neuroanat. 2021; 116: 101978.
  16. Shaer A, Azarpira N, Aghdaie MH, Esfandiari E. Isolation and characterization of human mesenchymal stromal cells derived from placental decidua basalis; umbilical cord wharton’s jelly and amniotic membrane. Pak J Med Sci. 2014; 30(5): 1022-1026.
  17. Nekoei SM, Azarpira N, Sadeghi L, Kamalifar S. In vitro differentiation of human umbilical cord Wharton’s jelly mesenchymal stromal cells to insulin producing clusters. World J Clin Cases. 2015; 3(7): 640-649.
  18. Cespi M, Bonacucina G, Pucciarelli S, Cocci P, Perinelli DR, Casettari L, et al. Evaluation of thermosensitive poloxamer 407 gel systems for the sustained release of estradiol in a fish model. Eur J Pharm Biopharm. 2014; 88(3): 954-961.
  19. Zhang Y, Wang X, Chen J, Qian D, Gao P, Qin T, et al. Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis. J Nanobiotechnology. 2022; 20(1): 56.
  20. Yang C, Lei D, Ouyang W, Ren J, Li H, Hu J, et al. Conditioned media from human adipose tissue-derived mesenchymal stem cells and umbilical cord-derived mesenchymal stem cells efficiently induced the apoptosis and differentiation in human glioma cell lines in vitro. Biomed Res Int. 2014; 2014: 109389.
  21. Noorafshan A, Asadi-Golshan R, Erfanizadeh M, Karbalay-Doust S. Beneficial effects of olive oil on the rats’ cerebellum: functional and structural evidence. Folia Med (Plovdiv). 2018; 60(3): 454-463.
  22. Oh HA, Kwak J, Kim BJ, Jin HJ, Park WS, Choi SJ, et al. Migration inhibitory factor in conditioned medium from human umbilical cord blood-derived mesenchymal stromal cells stimulates hair growth. Cells. 2020; 9(6): 1344.
  23. Deng W, Zhang Y, Wang W, Song A, Mukama O, Huang J, et al. Hair follicle-derived mesenchymal stem cells decrease alopecia areata mouse hair loss and reduce inflammation around the hair follicle. Stem Cell Res Ther. 2021; 12(1): 548.
  24. Sperling LC, Cowper SE, Knopp EA. An atlas of hair pathology with clinical correlations. 2nd ed. New York & London: Informa Healthcare; 2012: 216.
  25. Galbraith GM, Thiers BH. In vitro suppression of human lymphocyte activity by minoxidil. Int J Dermatol. 1985; 24(4): 249-251.
  26. Choi M, Choi SJ, Jang S, Choi HI, Kang BM, Hwang ST, et al. Shikimic acid, a mannose bioisostere, promotes hair growth with the induction of anagen hair cycle. Sci Rep. 2019; 9(1): 17008.
  27. Sintov A, Serafimovich S, Gilhar A. New topical antiandrogenic formulations can stimulate hair growth in human bald scalp grafted onto mice. Int J Pharm. 2000; 194(1): 125-134.
  28. Johnson DB, Sonthalia S. FlutamideSeries. In: StatPearls [Internet]. Stat-Pearls Publishing; 2021. Available from: https://www. (1 May 2023).
  29. Ramdasi S, Tiwari SK. Human mesenchymal stem cell-derived conditioned media for hair regeneration applications. J Stem Cells. 2016; 11(4): 201-211.
  30. Anudeep TC, Jeyaraman M, Muthu S, Rajendran RL, Gangadaran P, Mishra PC, et al. Advancing Regenerative Cellular Therapies in Non-Scarring Alopecia. Pharmaceutics. 2022; 14(3): 612.
  31. Lu H, Poirier C, Cook T, Traktuev DO, Merfeld-Clauss S, Lease B, et al. Conditioned media from adipose stromal cells limit lipopolysaccharide- induced lung injury, endothelial hyperpermeability and apoptosis. J Transl Med. 2015; 13: 67.
  32. Jung MK, Ha S, Huh SY, Park SB, Kim S, Yang Y, et al. Hair-growth stimulation by conditioned medium from vitamin D3-activated preadipocytes in C57BL/6 mice. Life Sci. 2015; 128: 39-46.
  33. Dong L, Hao H, Xia L, Liu J, Ti D, Tong C, et al. Treatment of MSCs with Wnt1a-conditioned medium activates DP cells and promotes hair follicle regrowth. Sci Rep. 2014; 4: 5432.
  34. Li M, Zhong L, He W, Ding Z, Hou Q, Zhao Y, et al. Concentrated conditioned medium-loaded silk nanofiber hydrogels with sustained release of bioactive factors to improve skin regeneration. ACS Appl Bio Mater. 2019; 2(10): 4397-4407.
  35. Stortelers C, Kerkhoven R, Moolenaar WH. Multiple actions of lysophosphatidic acid on fibroblasts revealed by transcriptional profiling. BMC Genomics. 2008; 9: 387.
  36. Fong CY, Tam K, Cheyyatraivendran S, Gan SU, Gauthaman K, Armugam A, et al. Human Wharton’s jelly stem cells and its conditioned medium enhance healing of excisional and diabetic wounds. J Cell Biochem. 2014; 115(2): 290-302.
  37. Liu C, Wang C, Yang F, Lu Y, Du P, Hu K, et al. The conditioned medium from mesenchymal stromal cells pretreated with proinflammatory cytokines promote fibroblasts migration and activation. PLoS One. 2022; 17(4): e0265049.
  38. Sauter LS, Weibel ER. Morphometric evaluation of skin structures by stereologic methods. Application to testosterone-treated rats. Dermatologica. 1971; 143(3): 174-183.
  39. Ban K, Bae S, Yoon YS. Current strategies and challenges for purification of cardiomyocytes derived from human pluripotent stem cells. Theranostics. 2017; 7(7): 2067-2077.
  40. Czarnecka A, Odziomek A, Murzyn M, Dubis J, Bagłaj-Oleszczuk M, Hryncewicz-Gwóźdź A. Wharton’s jelly-derived mesenchymal stem cells in the treatment of four patients with alopecia areata. Adv Clin Exp Med. 2021; 30(2): 211-218.