Background and Aims:Androgenetic alopecia (AGA) is a common form of hair
loss in both men and women. Despite its high prevalence and associated patient
morbidity, the approved therapeutic options are limited to finasteride and
minoxidil. The present study is aimed at assessing the efficacy of hair serum
formulation, Trichosera?containing Bone marrow-derived mesenchymal stromal
cells conditioned media as an active ingredient, for hair fall control and hair
regrowth in healthy Indian human volunteers. Methods:The product was made using a 20% concentration of
10X Conditioned Media along with excipients. The final product was tested for
physicochemical parameters, biomarkers, total protein content and microbial
limits as per our in-house specifications. Results:The primary irritation patch test showed that the
product is non-irritant and dermatologically safe. A clinical study on 40
subjects was conducted to evaluate the effectiveness of the bioactive formulation
in hair fall control and hair regrowth in healthy volunteers. Phototrichogram
measurement showed hair density and hair growth rate increased significantly by
11.54% and 18.66% at week 24. Hair tensile strength also increased significantly
by 41.10% at 12 weeks follow-up. Hair pull test, to see a reduction
in pulled hair and comb’s test to show a decrease
in hair fall
References
[1]
Lolli, F., Pallotti, F., Rossi, A., et al. (2017) Androgenetic Alopecia: A Review. Endocrinology, 57, 9-17. https://doi.org/10.1007/s12020-017-1280-y
[2]
Paus, R. and Cotsarelis, G. (1999) The Biology of Hair Follicles. The New England Journal of Medicine, 341, 491-497. https://doi.org/10.1056/NEJM199908123410706
[3]
Piérard-Franchimont, C. and Piérard, G.E. (2001) Teloptosis, a Turning Point in Hair Shedding Biorhythms. Dermatology, 203, 115-117. https://doi.org/10.1159/000051723
[4]
Khandpur, S., Suman, M. and Reddy, B.S. (2002) Comparative Efficacy of Various Treatment Regimens for Androgenetic Alopecia in Men. The Journal of Dermatology, 29, 489-498. https://doi.org/10.1111/j.1346-8138.2002.tb00314.x
[5]
Hajheydari, Z., Akbari, J., Saeedi, M. and Shokoohi, L. (2009) Comparing the Therapeutic Effects of Finasteride Gel and Tablet in Treatment of the Androgenetic Alopecia. Indian Journal of Dermatology, Venereology and Leprology, 75, 47-51. https://doi.org/10.4103/0378-6323.45220
[6]
Buhl, A.E., Waldon, D.J., Kawabe, T. and Holland, J.M. (1989) Minoxidil Stimulates Mouse Vibrissae Follicles in Organ Culture. Journal of Investigative Dermatology, 92, 315-320. https://doi.org/10.1111/1523-1747.ep12277095
[7]
Hyo, S.S., Chong, H.W., Seung, H.L., Oh, S.K., Kyu, H.K. and Hee, C.E. (2007) Efficacy of 5% Minoxidil versus Combined 5% Minoxidil and 0.01% Tretinoin for Male Pattern Hair Loss: A Randomized, Double-Blind, Comparative Clinical Trial. American Journal of Clinical Dermatology, 8, 285-290. https://doi.org/10.2165/00128071-200708050-00003
[8]
Yoo, B.Y., Shin, Y.H., Yoon, H.H., Seo, Y.K., Song, K.Y. and Park, J.K. (2010) Application of Mesenchymal Stem Cells Derived from Bone Marrow and Umbilical Cord in Human Hair Multiplication. Journal of Dermatological Science, 60, 74-83. https://doi.org/10.1016/j.jdermsci.2010.08.017
[9]
Kerure, A.S. and Patwardhan, N. (2018) Complications in Hair Transplantation. Journal of Cutaneous and Aesthetic Surgery, 11, 182-189.
[10]
Liang, X., Ding, Y., Zhang, Y., Tse, H.F. and Lian, Q. (2014) Paracrine Mechanisms of Mesenchymal Stem Cell-Based Therapy: Current Status and Perspectives. Cell Transplantation, 23, 1045-1059. https://doi.org/10.3727/096368913X667709
[11]
Wang, J., Liao, L. and Tan, J. (2011) Mesenchymal-Stem-Cell-Based Experimental and Clinical Trials: Current Status and Open Questions. Expert Opinion on Biological Therapy, 11, 893-909. https://doi.org/10.1517/14712598.2011.574119
[12]
Yi, T. and Song, S.U. (2012) Immunomodulatory Properties of Mesenchymal Stem Cells and Their Therapeutic Applications. Archives of Pharmacal Research, 35, 213-221. https://doi.org/10.1007/s12272-012-0202-z
[13]
Pawitan, J.A. (2014) Prospect of Stem Cell Conditioned Medium in Regenerative Medicine. BioMed Research International, 2014, Article ID: 965849. https://doi.org/10.1155/2014/965849
[14]
Ratajczak, M.Z., Kucia, M., Jadczyk, T., et al. (2011) Pivotal Role of Paracrine Effects in Stem Cell Therapies in Regenerative Medicine: Can We Translate Stem Cell-Secreted Paracrine Factors and Microvesicles into Better Therapeutic Strategies? Leuk, 26, 1166-1173. https://doi.org/10.1038/leu.2011.389
[15]
Deng, H., Sun, C., Sun, Y.X., et al. (2018) Lipid, Protein, and MicroRNA Composition within Mesenchymal Stem Cell-Derived Exosomes. Cellular Reprogramming, 20, 178-186. https://home.liebertpub.com/cell https://doi.org/10.1089/cell.2017.0047
[16]
Won, C.H., Park, G.H., Wu, X., et al. (2017) The Basic Mechanism of Hair Growth Stimulation by Adipose-Derived Stem Cells and Their Secretory Factors. Current Stem Cell Research and Therapy, 12, 535-543. https://doi.org/10.2174/1574888X12666170829161058
[17]
Shin, H., et al. (2017) Up-to-Date Clinical Trials of Hair Regeneration Using Conditioned Media of Adipose-Derived Stem Cells in Male and Female Pattern Hair Loss. Current Stem Cell Research and Therapy, 12, 524-530. https://doi.org/10.2174/1574888X12666170504120244
[18]
Shin, H., Ryu, H.H., Kwon, O., Park, B.S. and Jo, S.J. (2015) Clinical Use of Conditioned Media of Adipose Tissue-Derived Stem Cells in Female Pattern Hair Loss: A Retrospective Case Series Study. International Journal of Dermatology, 54, 730-735. https://doi.org/10.1111/ijd.12650
[19]
Narita, K., Fukuoka, H., Sekiyama, T., Suga, H. and Harii, K. (2020) Sequential Scalp Assessment in Hair Regeneration Therapy Using an Adipose-Derived Stem Cell-Conditioned Medium. Dermatologic Surgery, 46, 819-825. https://doi.org/10.1097/DSS.0000000000002128
[20]
Fukuoka, H. and Suga, H. (2015) Hair Regeneration Treatment Using Adipose-Derived Stem Cell Conditioned Medium: Follow-Up with Trichograms. Eplasty, 15, e10.
[21]
Balasubramanian, S., Thej, C., Walvekar, A., et al. (2017) Evaluation of the Secretome Profile and Functional Characteristics of Human Bone Marrow Mesenchymal Stromal Cells-Derived Conditioned Medium Suggest Potential for Skin Rejuvenation. Journal of Cosmetics, Dermatological Sciences and Applications, 7, 99-117. https://doi.org/10.4236/jcdsa.2017.71010
[22]
Ramdasi, S. (2016) Growth Factors and Cytokines Secreted in Conditioned Media by Mesenchymal Stem Cells-Promising Possible Therapeutic Approach for Hair Regeneration. International Journal of Biosciences, 6, 9-19.
[23]
Gupta, P.K., Krishna, M., Chullikana, A., et al. (2017) Administration of Adult Human Bone Marrow-Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger’s Disease: Phase II Study Report Suggests Clinical Efficacy. Stem Cells Translational Medicine, 6, 689-699. https://doi.org/10.5966/sctm.2016-0237
[24]
Sachdev, M., Chullikana, A., Seetharam, R.N., et al. (2017) A Single Arm, Monocentric, Prospective, Open Label Study to Evaluate Anti-Ageing Efficacy of Human Growth Factors and Cytokines Containing Cosmetic Skin Serum in Indian Female Population. Journal of Cosmetics, Dermatological Sciences and Applications, 7, 118-132. https://doi.org/10.4236/jcdsa.2017.71011
[25]
Bhat, S., Amirthalingam, M., Ballambat, S.P., et al. (2021) Novel Bioactive Formulation Derived from the Conditioned Medium of Mesenchymal Stromal Cells Reduces Under-Eye Dark Circles in Human Volunteers. Journal of Cosmetic Dermatology, 21, 814-826. https://doi.org/10.1111/jocd.14145
[26]
Pal, R., Hanwate, M., Jan, M. and Totey, S. (2009) Phenotypic and Functional Comparison of Optimum Culture Conditions for Upscaling of Bone Marrow-Derived Mesenchymal Stem Cells. Journal of Tissue Engineering and Regenerative Medicine, 3, 163-174. https://doi.org/10.1002/term.143
[27]
Levy, L.L. and Emer, J.J. (2013) Female Pattern Alopecia: Current Perspectives. International Journal of Women’s Health, 5, 541-556. https://doi.org/10.2147/IJWH.S49337
[28]
Traish, A.M. (2020) Health Risks Associated with Long-Term Finasteride and Dutasteride Use: It’s Time to Sound the Alarm. The World Journal of Men’s Health, 38, 323-337. https://doi.org/10.5534/wjmh.200012
[29]
Traish, A.M., Mulgaonkar, A. and Giordano, N. (2014) The Dark Side of 5α-Reductase Inhibitors'Therapy: Sexual Dysfunction, High Gleason Grade Prostate Cancer and Depression. Korean Journal of Urology, 55, 367-379. https://doi.org/10.4111/kju.2014.55.6.367
[30]
Yu, W., Wang, J. and Yin, J. (2011) Platelet-Rich Plasma: A Promising Product for Treatment of Peripheral Nerve Regeneration after Nerve Injury. International Journal of Neuroscience, 121, 176-180. https://doi.org/10.3109/00207454.2010.544432
[31]
Borrione, P., Di Gianfrancesco, A., Pereira, M.T. and Pigozzi, F. (2010) Platelet-Rich Plasma in Muscle Healing. American Journal of Physical Medicine & Rehabilitation, 89, 854-861. https://doi.org/10.1097/PHM.0b013e3181f1c1c7
[32]
Gentile, P. and Garcovich, S. (2019) Advances in Regenerative Stem Cell Therapy in Androgenic Alopecia and Hair Loss: Wnt Pathway, Growth-Factor, and Mesenchymal Stem Cell Signaling Impact Analysis on Cell Growth and Hair Follicle Development. Cells, 8, Article No. 466. https://doi.org/10.3390/cells8050466
[33]
Jha, A.K., Udayan, U.K., Roy, P.K., Amar, A.K.J. and Chaudhary, R.K.P. (2018) Original Article: Platelet-Rich Plasma with Microneedling in Androgenetic Alopecia along with Dermoscopic Pre- and Post-Treatment Evaluation. Journal of Cosmetic Dermatology, 17, 313-318. https://doi.org/10.1111/jocd.12394
[34]
Singh, S. (2015) Role of Platelet-Rich Plasma in Chronic Alopecia Areata: Our Centre Experience. Indian Journal of Plastic Surgery, 48, 57-59. https://doi.org/10.4103/0970-0358.155271
[35]
Badran, K.W. and Sand, J.P. (2018) Platelet-Rich Plasma for Hair Loss: Review of Methods and Results. Facial Plastic Surgery Clinics of North America, 26, 469-485. https://doi.org/10.1016/j.fsc.2018.06.008
[36]
York, K., Meah, N., Bhoyrul, B. and Sinclair, R. (2020) A Review of the Treatment of Male Pattern Hair Loss. Expert Opinion on Pharmacotherapy, 21, 603-612. https://doi.org/10.1080/14656566.2020.1721463
[37]
Lee, Y.I., Kim, J., Kim, J., Park, S. and Lee, J.H. (2020) The Effect of Conditioned Media from Human Adipocyte-Derived Mesenchymal Stem Cells on Androgenetic Alopecia after Nonablative Fractional Laser Treatment. Dermatologic Surgery, 46, 1698-1704. https://doi.org/10.1097/DSS.0000000000002518
[38]
Oh, H.A., Kwak, J., Kim, B.J., et al. (2020) Migration Inhibitory Factor in Conditioned Medium from Human Umbilical Cord Blood-Derived Mesenchymal Stromal Cells Stimulates Hair Growth. Cells, 9, Article No. 1344. https://doi.org/10.3390/cells9061344
[39]
Tomita, Y., Akiyama, M. and Shimizu, H. (2006) PDGF Isoforms Induce and Maintain Anagen Phase of Murine Hair Follicles. Journal of Dermatological Science, 43, 105-115. https://doi.org/10.1016/j.jdermsci.2006.03.012
[40]
Lee, Y.R., Yamazaki, M., Mitsui, S., Tsuboi, R. and Ogawa, H. (2001) Hepatocyte Growth Factor (HGF) Activator Expressed in Hair Follicles Is Involved in in Vitro HGF-Dependent Hair Follicle Elongation. Journal of Dermatological Science, 25, 156-163. https://doi.org/10.1016/S0923-1811(00)00124-9
[41]
Yano, K., Brown, L.F. and Detmar, M. (2001) Control of Hair Growth and Follicle Size by VEGF-Mediated Angiogenesis. Journal of Clinical Investigation, 107, 409-417. https://doi.org/10.1172/JCI11317
[42]
Lin, W., Xiang, L.-J., Shi, H.-X., et al. (2015) Fibroblast Growth Factors Stimulate Hair Growth through β-Catenin and Shh Expression in C57BL/6 Mice. BioMed Research International, 2015, Article ID: 730139. https://doi.org/10.1155/2015/730139
[43]
Gunawardena, T.N.A., Rahman, M.T., Abdullah, B.J.J. and Abu Kasim, N.H. (2019) Conditioned Media Derived from Mesenchymal Stem Cell Cultures: The Next Generation for Regenerative Medicine. Journal of Tissue Engineering and Regenerative Medicine, 13, 569-586. https://doi.org/10.1002/term.2806
[44]
Won, C.H., Yoo, H.G., Kwon, O.S., et al. (2010) Hair Growth Promoting Effects of Adipose Tissue-Derived Stem Cells. Journal of Dermatological Science, 57, 134-137. https://doi.org/10.1016/j.jdermsci.2009.10.013
[45]
Xiao, S., Deng, Y., Mo, X., et al. (2020) Promotion of Hair Growth by Conditioned Medium from Extracellular Matrix/Stromal Vascular Fraction Gel in C57BL/6 Mice. Stem Cells International, 2020, Article ID: 9054514. https://doi.org/10.1155/2020/9054514
[46]
Tak, Y.J., Lee, S.Y., Cho, A.R. and Kim, Y.S. (2020) A Randomized, Double-Blind, Vehicle-Controlled Clinical Study of Hair Regeneration Using Adipose-Derived Stem Cell Constituent Extract in Androgenetic Alopecia. Stem Cells Translational Medicine, 9, 839-849. https://doi.org/10.1002/sctm.19-0410
[47]
Osugi, M., Katagiri, W., Yoshimi, R., Inukai, T., Hibi, H. and Ueda, M. (2012) Conditioned Media from Mesenchymal Stem Cells Enhanced Bone Regeneration in Rat Calvarial Bone Defects. Tissue Engineering Part A, 18, 1479-1489. https://doi.org/10.1089/ten.tea.2011.0325
[48]
Maguire, G. (2013) Stem Cell Therapy without the Cells. Communicative & Integrative Biology, 6, e26631. https://doi.org/10.4161/cib.26631
[49]
Park, B.S., Kim, W.S., Choi, J.S., et al. (2010) Hair Growth Stimulated by Conditioned Medium of Adipose-Derived Stem Cells Is Enhanced by Hypoxia: Evidence of Increased Growth Factor Secretion. Biomedical Research, 31, 27-34. https://doi.org/10.2220/biomedres.31.27
[50]
Bermudez, M.A., Sendon-Lago, J., Seoane, S., et al. (2016) Anti-Inflammatory Effect of Conditioned Medium from Human Uterine Cervical Stem Cells in Uveitis. Experimental Eye Research, 149, 84-92. https://doi.org/10.1016/j.exer.2016.06.022
[51]
Eiró, N., Sendon-Lago, J., Seoane, S., et al. (2014) Potential Therapeutic Effect of the Secretome from Human Uterine Cervical Stem Cells against both Cancer and Stromal Cells Compared with Adipose Tissue Stem Cells. Oncotarget, 5, 10692-10708. https://doi.org/10.18632/oncotarget.2530
[52]
Spees, J.L., Gregory, C.A., Singh, H., et al. (2004) Internalized Antigens Must Be Removed to Prepare Hypoimmunogenic Mesenchymal Stem Cells for Cell and Gene Therapy. Molecular Therapy, 9, 747-756. https://doi.org/10.1016/j.ymthe.2004.02.012
[53]
Olsen, E.A., Dunlap, F.E., Funicella, T., et al. (2002) A Randomized Clinical Trial of 5% Topical Minoxidil versus 2% Topical Minoxidil and Placebo in the Treatment of Androgenetic Alopecia in Men. Journal of the American Academy of Dermatology, 47, 377-385. https://doi.org/10.1067/mjd.2002.124088
[54]
Kaufman, K.D., Olsen, E.A., Whiting, D., et al. (1998) Finasteride in the Treatment of Men with Androgenetic Alopecia. Finasteride Male Pattern Hair Loss Study Group. Journal of the American Academy of Dermatology, 39, 578-589.
[55]
Choi, N., Shin, S., Song, S.U. and Sung, J.H. (2018) Minoxidil Promotes Hair Growth through Stimulation of Growth Factor Release from Adipose-Derived Stem Cells. International Journal of Molecular Sciences, 19, Article No. 691. https://doi.org/10.3390/ijms19030691
[56]
Kawashima, M., Hayashi, N., Igarashi, A., et al. (2004) Finasteride in the Treatment of Japanese Men with Male Pattern Hair Loss. European Journal of Dermatology, 14, 247-254. http://www.ncbi.nlm.nih.gov/pubmed/15319158
