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In vitro evaluation of the effects of human umbilical cord extracts on human fibroblasts, keratinocytes, and melanocytes

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Abstract

Skin aging is the result of internal and external factors. So-called photoaging has been identified as the major factor in skin aging. Effects of photoaging include inhibition of fibroblast and keratinocyte proliferation as well as collagen and fibronectin expression, while activating expression of collagenases such as matrix metalloproteinase-1. Previous studies have shown that extracts or products from human placenta significantly improve skin aging and chronic wound healing. However, there are few studies of umbilical cord extracts. Therefore, this study aimed to evaluate the effects of umbilical cord extract-derived formulae on three kinds of skin cells including fibroblasts, keratinocytes, and melanocytes. We prepared 20 formulae from intracellular umbilical cord extracts, extracellular umbilical cord extracts, and umbilical cord-derived stem cell extracts, as well as five control formulae. We evaluated the effects of the 25 formulae on fibroblast and keratinocyte proliferation, and expression of collagen I, fibronectin, and matrix metalloproteinase-1 in fibroblasts and tyrosinase in melanocytes. The results showed that 7.5% formula 35 was the most effective formula for promotion of fibroblast and keratinocyte proliferation. At this concentration, formula 35 also induced collagen expression and inhibited matrix metalloproteinase-1 expression at the transcriptional level. However, this formula had no effect on tyrosinase expression in melanocytes. These results demonstrate that umbilical cord extracts can serve as an attractive source of proteins for skincare and chronic wound healing products.

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References

  • Agar N.; Young A. R. Melanogenesis: a photoprotective response to DNA damage? Mutat. Res. 571: 121–132; 2005.

    Article  PubMed  CAS  Google Scholar 

  • Alvares O.; Klebe R.; Grant G.; Cochran D. L. Growth factor effects on the expression of collagenase and TIMP-1 in periodontal ligament cells. J. Periodontol. 66: 552–558; 1995.

    Article  PubMed  CAS  Google Scholar 

  • Angel P.; Szabowski A.; Schorpp-Kistner M. Function and regulation of AP-1 subunits in skin physiology and pathology. Oncogene 20: 2413–2423; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Blumenberg M. Profiling and meta-analysis of epidermal keratinocytes responses to epidermal growth factor. BMC Genomics 14: 85; 2013.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cho H. R.; Ryou J. H.; Lee J. W.; Lee M. H. The effects of placental extract on fibroblast proliferation. J. Cosmet. Sci. 59: 195–202; 2008.

    PubMed  CAS  Google Scholar 

  • Chung K. Y.; Agarwal A.; Uitto J.; Mauviel A. An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta. J. Biol. Chem. 271: 3272–3278; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Claudinot S.; Nicolas M.; Oshima H.; Rochat A.; Barrandon Y. Long-term renewal of hair follicles from clonogenic multipotent stem cells. Proc. Natl. Acad. Sci. U. S. A. 102: 14677–14682; 2005.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Datta P.; Bhattacharyya D. Spectroscopic and chromatographic evidences of NADPH in human placental extract used as wound healer. J. Pharm. Biomed. Anal. 34: 1091–1098; 2004.

    Article  PubMed  CAS  Google Scholar 

  • De D.; Datta Chakraborty P.; Mitra J.; Sharma K.; Mandal S.; Das A.; Chakrabarti S.; Bhattacharyya D. Ubiquitin-like protein from human placental extract exhibits collagenase activity. PloS One 8: e59585; 2013.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dorronsoro A.; Robbins P. D. Regenerating the injured kidney with human umbilical cord mesenchymal stem cell-derived exosomes. Stem Cell Res. Ther. 4: 39; 2013.

    Article  PubMed Central  PubMed  Google Scholar 

  • Fisher G. J.; Datta S.; Wang Z.; Li X. Y.; Quan T.; Chung J. H.; Kang S.; Voorhees J. J. c-Jun-dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoic acid. J. Clin. Invest. 106: 663–670; 2000.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Fisher G. J.; Talwar H. S.; Lin J.; Lin P.; McPhillips F.; Wang Z.; Li X.; Wan Y.; Kang S.; Voorhees J. J. Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo. J. Clin. Invest. 101: 1432–1440; 1998.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Garrington T. P.; Johnson G. L. Organization and regulation of mitogen-activated protein kinase signaling pathways. Curr. Opin. Cell Biol. 11: 211–218; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez R.; Griparic L.; Umana M.; Burgee K.; Vargas V.; Nasrallah R.; Silva F.; Patel A. An efficient approach to isolation and characterization of pre- and postnatal umbilical cord lining stem cells for clinical applications. Cell Transplant. 19: 1439–1449; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Grichnik J. M.; Ali W. N.; Burch J. A.; Byers J. D.; Garcia C. A.; Clark R. E.; Shea C. R. KIT expression reveals a population of precursor melanocytes in human skin. J. Invest. Dermatol. 106: 967–971; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Hao H.; Chen G.; Liu J.; Ti D.; Zhao Y.; Xu S.; Fu X.; Han W. Culturing on Wharton’s jelly extract delays mesenchymal stem cell senescence through p53 and p16INK4a/pRb pathways. PloS One 8: e58314; 2013.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hong J. W.; Lee W. J.; Hahn S. B.; Kim B. J.; Lew D. H. The effect of human placenta extract in a wound healing model. Ann. Plast. Surg. 65: 96–100; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Hornebeck W. Down-regulation of tissue inhibitor of matrix metalloprotease-1 (TIMP-1) in aged human skin contributes to matrix degradation and impaired cell growth and survival. Pathologie-biologie 51: 569–573; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Ito M.; Liu Y.; Yang Z.; Nguyen J.; Liang F.; Morris R. J.; Cotsarelis G. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat. Med. 11: 1351–1354; 2005.

    Article  PubMed  CAS  Google Scholar 

  • Ito M.; Yang Z.; Andl T.; Cui C.; Kim N.; Millar S. E.; Cotsarelis G. Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447: 316–320; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Jo C. H.; Kim O. S.; Park E. Y.; Kim B. J.; Lee J. H.; Kang S. B.; Lee J. H.; Han H. S.; Rhee S. H.; Yoon K. S. Fetal mesenchymal stem cells derived from human umbilical cord sustain primitive characteristics during extensive expansion. Cell Tissue Res. 334: 423–433; 2008.

    Article  PubMed  Google Scholar 

  • Karin M.; Liu Z.; Zandi E. AP-1 function and regulation. Curr. Opin. Cell Biol. 9: 240–246; 1997.

    Article  PubMed  CAS  Google Scholar 

  • Kawakatsu M.; Urata Y.; Goto S.; Ono Y.; Li T. S. Placental extract protects bone marrow-derived stem/progenitor cells against radiation injury through anti-inflammatory activity. J. Radiat. Res. 54: 268–276; 2013.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kim J. H.; Jung M.; Kim H. S.; Kim Y. M.; Choi E. H. Adipose-derived stem cells as a new therapeutic modality for ageing skin. Exp. Dermatol. 20: 383–387; 2011.

    Article  PubMed  CAS  Google Scholar 

  • Kim W. S.; Park B. S.; Sung J. H.; Yang J. M.; Park S. B.; Kwak S. J.; Park J. S. Wound healing effect of adipose-derived stem cells: a critical role of secretory factors on human dermal fibroblasts. J. Dermatol. Sci. 48: 15–24; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Kim Y. S.; Park J. J.; Sakoda Y.; Zhao Y.; Hisamichi K.; Kaku T.; Tamada K. Preventive and therapeutic potential of placental extract in contact hypersensitivity. Int. Immunopharmacol. 10: 1177–1184; 2010.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kisselbach L.; Merges M.; Bossie A.; Boyd A. CD90 Expression on human primary cells and elimination of contaminating fibroblasts from cell cultures. Cytotechnology 59: 31–44; 2009.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kita K.; Gauglitz G. G.; Phan T. T.; Herndon D. N.; Jeschke M. G. Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells Dev. 19: 491–502; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Lee K. H.; Kim T. H.; Lee W. C.; Kim S. H.; Lee S. Y.; Lee S. M. Anti-inflammatory and analgesic effects of human placenta extract. Nat. Prod. Res. 25: 1090–1100; 2011.

    Article  PubMed  CAS  Google Scholar 

  • Mallick S.; Singh S. K.; Sarkar C.; Saha B.; Bhadra R. Human placental lipid induces melanogenesis by increasing the expression of tyrosinase and its related proteins in vitro. Pigment cell research/sponsored by the European Society for Pigment Cell Research and the International. Pigment Cell Soc. 18: 25–33; 2005.

    Article  CAS  Google Scholar 

  • Massague J. How cells read TGF-beta signals. Nat. Rev. Mol. Cell Biol. 1: 169–178; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Meyer M.; Muller A. K.; Yang J.; Moik D.; Ponzio G.; Ornitz D. M.; Grose R.; Werner S. FGF receptors 1 and 2 are key regulators of keratinocyte migration in vitro and in wounded skin. J. Cell Sci. 125: 5690–5701; 2012.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Montanucci P.; Basta G.; Pescara T.; Pennoni I.; Di Giovanni F.; Calafiore R. New simple and rapid method for purification of mesenchymal stem cells from the human umbilical cord Wharton jelly. Tissue Eng. A 17: 2651–2661; 2011.

    Article  CAS  Google Scholar 

  • Nath S.; Bhattacharyya D. Cell adhesion by aqueous extract of human placenta used as wound healer. Indian J. Exp. Biol. 45: 732–738; 2007.

    PubMed  Google Scholar 

  • Norris A.; Todd C.; Graham A.; Quinn A. G.; Thody A. J. The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo. Br. J. Dermatol. 134: 299–306; 1996.

    Article  PubMed  CAS  Google Scholar 

  • O’Keefe E. J.; Payne R. E.; Russell N. Keratinocyte growth-promoting activity from human placenta. J. Cell. Physiol. 124: 439–445; 1985.

    Article  PubMed  Google Scholar 

  • Pal P.; Mallick S.; Mandal S. K.; Das M.; Dutta A. K.; Datta P. K.; Bera R.; Bhadra R. A human placental extract: in vivo and in vitro assessments of its melanocyte growth and pigment-inducing activities. Int. J. Dermatol. 41: 760–767; 2002.

    Article  PubMed  Google Scholar 

  • Phuc P. V.; Nhung T. H.; Loan D. T.; Chung D. C.; Ngoc P. K. Differentiating of banked human umbilical cord blood-derived mesenchymal stem cells into insulin-secreting cells. In Vitro Cell. Dev. Biol. Anim. 47: 54–63; 2011.

    Article  PubMed  CAS  Google Scholar 

  • Quan T.; He T.; Voorhees J. J.; Fisher G. J. Ultraviolet irradiation blocks cellular responses to transforming growth factor-beta by down-regulating its type-II receptor and inducing Smad7. J. Biol. Chem. 276: 26349–26356; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Redondo P.; Garcia-Foncillas J.; Okroujnov I.; de Felipe I.; Quintanilla E. CD24 expression on human keratinocytes. Exp. Dermatol. 7: 175–178; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Reinisalo M.; Putula J.; Mannermaa E.; Urtti A.; Honkakoski P. Regulation of the human tyrosinase gene in retinal pigment epithelium cells: the significance of transcription factor orthodenticle homeobox 2 and its polymorphic binding site. Mol. Vis. 18: 38–54; 2012.

    PubMed Central  PubMed  CAS  Google Scholar 

  • Reza H. M.; Ng B. Y.; Gimeno F. L.; Phan T. T.; Ang L. P. Umbilical cord lining stem cells as a novel and promising source for ocular surface regeneration. Stem Cell Rev. 7: 935–947; 2011a.

    Article  PubMed  Google Scholar 

  • Reza H. M.; Ng B. Y.; Phan T. T.; Tan D. T.; Beuerman R. W.; Ang L. P. Characterization of a novel umbilical cord lining cell with CD227 positivity and unique pattern of P63 expression and function. Stem Cell Rev. 7: 624–638; 2011b.

    Article  PubMed  CAS  Google Scholar 

  • Rittie L.; Fisher G. J. UV-light-induced signal cascades and skin aging. Ageing Res. Rev. 1: 705–720; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Saha B.; Singh S. K.; Sarkar C.; Mallick S.; Bera R.; Bhadra R. Transcriptional activation of tyrosinase gene by human placental sphingolipid. Glycoconj. J. 23: 259–268; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Salehinejad P.; Alitheen N. B.; Ali A. M.; Omar A. R.; Mohit M.; Janzamin E.; Samani F. S.; Torshizi Z.; Nematollahi-Mahani S. N. Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton’s jelly. In Vitro Cell. Dev. Biol. Anim. 48: 75–83; 2012.

    Article  PubMed  Google Scholar 

  • Sarkar C.; Singh S. K.; Mandal S. K.; Saha B.; Bera R.; Ratha J.; Datta P. K.; Bhadra R. Human placental protein/peptides stimulate melanin synthesis by enhancing tyrosinase gene expression. Mol. Cell. Biochem. 285: 133–142; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Shukla V. K.; Rasheed M. A.; Kumar M.; Gupta S. K.; Pandey S. S. A trial to determine the role of placental extract in the treatment of chronic non-healing wounds. J. Wound Care 13: 177–179; 2004.

    PubMed  CAS  Google Scholar 

  • Singh S. K.; Sarkar C.; Mallick S.; Saha B.; Bera R.; Bhadra R. Human placental lipid induces melanogenesis through p38 MAPK in B16F10 mouse melanoma. Pigment cell research/sponsored by the European Society for Pigment Cell Research and the International. Pigment Cell Soc. 18: 113–121; 2005.

    Article  CAS  Google Scholar 

  • Sobolewski K.; Malkowski A.; Bankowski E.; Jaworski S. Wharton’s jelly as a reservoir of peptide growth factors. Placenta 26: 747–752; 2005.

    Article  PubMed  CAS  Google Scholar 

  • Song S. Y.; Jung J. E.; Jeon Y. R.; Tark K. C.; Lew D. H. Determination of adipose-derived stem cell application on photo-aged fibroblasts, based on paracrine function. Cytotherapy 13: 378–384; 2011.

    Article  PubMed  CAS  Google Scholar 

  • Sternlicht M. D.; Werb Z. How matrix metalloproteinases regulate cell behavior. Annu. Rev. Cell Dev. Biol. 17: 463–516; 2001.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tiwary S. K.; Shukla D.; Tripathi A. K.; Agrawal S.; Singh M. K.; Shukla V. K. Effect of placental-extract gel and cream on non-healing wounds. J. Wound Care 15: 325–328; 2006.

    PubMed  CAS  Google Scholar 

  • Togashi S.; Takahashi N.; Iwama M.; Watanabe S.; Tamagawa K.; Fukui T. Antioxidative collagen-derived peptides in human-placenta extract. Placenta 23: 497–502; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Tong C. K.; Vellasamy S.; Tan B. C.; Abdullah M.; Vidyadaran S.; Seow H. F.; Ramasamy R. Generation of mesenchymal stem cell from human umbilical cord tissue using a combination enzymatic and mechanical disassociation method. Cell Biol. Int. 35: 221–226; 2011.

    Article  PubMed  CAS  Google Scholar 

  • Welker P.; Schadendorf D.; Artuc M.; Grabbe J.; Henz B. M. Expression of SCF splice variants in human melanocytes and melanoma cell lines: potential prognostic implications. Br. J. Cancer 82: 1453–1458; 2000.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Xiao L.; Du Y.; Shen Y.; He Y.; Zhao H.; Li Z. TGF-beta 1 induced fibroblast proliferation is mediated by the FGF-2/ERK pathway. Front. Biosci. 17: 2667–2674; 2012.

    Article  CAS  Google Scholar 

  • Yu D.; Sun X.; Fang S.; Cao Z.; Meng K.; Ding Y. Validation of endothelial progenitor cells in human umbilical veins and the isolated endothelial cells. Endothelium 14: 141–150; 2007.

    Article  PubMed  CAS  Google Scholar 

  • Zhang H.; Zhang B.; Tao Y.; Cheng M.; Hu J.; Xu M.; Chen H. Isolation and characterization of mesenchymal stem cells from whole human umbilical cord applying a single enzyme approach. Cell Biochem. Funct. 30: 643–649; 2012.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Phuc Van Pham, Loan Thi-Tung Dang & Ngoc Kim Phan

  2. Mekostem Bank, Mekophar Chemical Pharmaceutical Joint-Stock Company, Ho Chi Minh, Vietnam

    Uyen Thanh Dinh, Huyen Thi-Thu Truong, Ba Ngoc Huynh & Dong Van Le

  3. Department of Immunology, Vietnam Military Medical University, 104 Phung Hung, Ha Dong, Ha Noi, Vietnam

    Dong Van Le

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  1. Phuc Van Pham
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  2. Loan Thi-Tung Dang
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  3. Uyen Thanh Dinh
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Correspondence to Phuc Van Pham.

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Van Pham, P., Dang, L.TT., Dinh, U.T. et al. In vitro evaluation of the effects of human umbilical cord extracts on human fibroblasts, keratinocytes, and melanocytes. In Vitro Cell.Dev.Biol.-Animal 50, 321–330 (2014). https://doi.org/10.1007/s11626-013-9706-1

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