The role of stem cell metabolites derived from placenta for skin regeneration: An in vitro study

Purwati Sumorejo , Muhammad Yulianto Listiawan, Ardhiah Iswanda Putri, Fedik Abdul Rantam, Helen Susilowati, Eryk Hendrianto

Purwati Sumorejo
Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia. Email: purwatisumorejo@gmail.com

Muhammad Yulianto Listiawan
Surabaya Regenerative Medicine Center, Dr. Soetomo General Hospital, Surabaya, Indonesia

Ardhiah Iswanda Putri
Plastic and Reconstructive Surgery Residency Program, Dr. Soetomo General Hospital, Surabaya, Indonesia

Fedik Abdul Rantam
Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia

Helen Susilowati
Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia

Eryk Hendrianto
Stem Cell Research and Development Center, Airlangga University, Surabaya, Indonesia
Online First: April 01, 2019 | Cite this Article
Sumorejo, P., Listiawan, M., Putri, A., Rantam, F., Susilowati, H., Hendrianto, E. 2019. The role of stem cell metabolites derived from placenta for skin regeneration: An in vitro study. Bali Medical Journal 8(1): 354-359. DOI:10.15562/bmj.v8i1.1387

Background: The role of stem cells in skin aging is to repair injured tissue or replace other cells in programmed cell death. Stem cell metabolites are rich in growth factors including IL-10, IL-4, EGF, GM-CSF, and TGF-β that can induce the skin production of protein and elastic fibers, leading to the improvement of skin appearance.

Aim: This study aimed to assess the characteristics of stem cell metabolites in vitro.

Methods: Cytotoxicity assay was performed using MTT reagents and optical cell densities were determined using ELISA reader to find the percentage of living cells. Cytokine detection assay was performed by analyzing the cytokine levels in the peripheral blood mononuclear cell (PBMC) and mesenchymal stem cell (MSC) using ELISA. Apoptosis assay was performed using the double staining method with the markers identified were Hsp70, p53, and caspase-3.

Results: All samples showed the percentage of living cells that exceed 70%. Cytokine detection assay showed a decrease of IL-12 and IFN-γ in both PBMC and MSC groups. The apoptosis assay of human adipose mesenchymal stem cells using a fluorescence microscope showed most of the green light was lost in control cells without metabolites. We found that the expressions of Hsp70 were increased while the expression of p53 and caspase-3 were decreased in the stem cell metabolites samples.

Conclusion: These results showed that stem cell metabolites are non-toxic, do not cause a systemic immune response to surrounding tissue, and able to inhibit the occurrence of apoptosis.


Lopez-Otin C, Blasco M.A, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217.

Hayflick L. Biological aging is no longer an unsolved problem. Ann N Y Acad Sci. 2007;1100():1-13.

Wensink MJ, van Heemst D, Rozing MP, Westendorp RG. The maintenance gap: a new theoretical perspective on the evolution of aging. Biogerontology. 2012:197-201.

Vaupel JW. Biodemography of human aging. Nature. 2010; 464(7288):536-42.

Purwati, Fedik. A.R, Sony Wibisono, Anas P, Eric H, Helen S, Deya K. Autologous MSC bone marrow stem cell and allogenic pancreatic stem cell for repair of beta pancreatic cell in experimental diabetes mellitus. African Journal of Internal Medicine. 2012;1(1):010-016.

Rantam FA, Ferdiansyah, Nasronudin, Purwati. Stem Cell Exploration, Isolation, and Methods. Surabaya Airlangga University Press. 2009.

Yang JA, Chung HM. Potential Application of Adipose-Derived Stem Cells and Their Secretory Factor to Skin: Discussion from Both Clinical and Industrial Viewpoint. Expert Opinion Biol Therapy. 2010;10(4):495-503.

Harris, Edward D. Biochemical Facts Behind The Definition and Properties of Metabolites. Biochemistry and Biophysics and Faculty of Nutrition Texas A&M University. 2017.

Ng Shyh-Chang, George Q, Daley, Lewis C. Cantley. Stem Cell Metabolism in Tissue Development and Aging. Development. 2013;140(12):2535–2547.

Lu W, Casanueva MO, Mahowald AP, Kato M, Lauterbach D, Ferguson EL. Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. PLoS Biol. 2012;10(7):e1001357.

Stockert JC, Blázquez-Castro A, Cañete M, Horobin RW, Villanueva A. MTT assay for cell viability: Intracellular localization of the formazan product is in lipid droplets. Acta Histochem. 2012;114(8):785-96.

van Tonder A, Joubert AM, Cromarty AD. Limitations of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay when compared to three commonly used cell enumeration assays. BMC Research Notes. 2015;8:47.

Kuete V, KaraosmanoÄŸlu O, Sivas H. Chapter 10 - Anticancer Activities of African Medicinal Spices and Vegetables. Medicinal Spices and Vegetables from Africa Therapeutic Potential Against Metabolic, Inflammatory, Infectious and Systemic Diseases. 2017:271-297.

Hiasa M, Abe M, Nakano A, Oda A, Amou H, Kido S, Takeuchi K, Kagawa K, Yata K, Hashimoto T, Ozaki S, Asaoka K, Tanaka E, Moriyama K, Matsumoto T. GM-CSF and IL-4 Induce Dendritic Cell Differentiation and Disrupt Osteoclastogenesis through M-CSF Receptor Shedding by Up-Regulation of TNF-Alpha Converting Enzyme (TACE). Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medical Sciences. 2010.

Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo J-L, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ. Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites. Science. 2009;325:612-616.

Ihsan F, Setyawan I, Satrio S, Jayanti AD, Tito S, Herningtyas EH. Ekstrak Purwaceng (Pimpinella alpinna) sebagai Agen Kemopreventif dan Kemoterapi Kanker Paru (Kajian Antiproliferatif serta Uji Apoptosis melalui Jalur P53,Bcl-2,Rb dan Caspase-9). Universitas Gadjah Mada. 2016.

Lee HJ, Lee EG, Kang S, Sung JH, Chung HM, Kim DH. Efficacy of Microneedling Plus Human Stem Cell Conditioned Medium for Skin Rejuvenation: A Randomized, Controlled, Blinded Split-Face Study. Ann Dermatol. 2014;26(5):584-591.

Subakir SB, Santosa DIS, Arleni. Kadar MDA dan HSP 70 pada Plasenta Penderita Preeklampsia. Makara Kesehatan. 2008;12(2):92-94.

No Supplementary Material available for this article.
Article Views      : 0
PDF Downloads : 0