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Stem cell recruitment factors secreted from cord blood-derived stem cells that are not secreted from mature endothelial cells enhance wound healing

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Abstract

Wounds are one of the most frequently occurring medical complication. Stem cells were recently highlighted as a novel therapeutic approach to treating wounds, although some negative aspects of allogenic stem cell transplantation were observed, such as cellular source limitations and unknown side effects in vivo. To address and eliminate these side effects, we examined the wound healing effect of secretory factors released from human cord blood-derived stem cells (hCB-SCs) and human umbilical vascular endothelial cells (HUVECs) on cutaneous excisional wound models. The hCB-SCs retained endothelial progenitor cell characteristics and expressed MSC markers such as CD73, CD105, and CD44. Analysis of hCB-SC-conditioned medium (CM) indicated that hCB-SCs secrete distinctly unique cytokines and chemokines such as TGF-β, PDGF, bFGF, EGF, KGF, and VEGF, which are well known to be important in normal angiogenesis and wound healing. Furthermore, hCB-SCs also secreted stem cell-recruiting factors such as G-CSF and GM-CSF, whereas HUVECs did not. When CB-SC-CM was applied to wound sites, hCB-SC-CM accelerated the wound healing rate compared with HUVEC-CM- and control medium-treated groups. In addition, hCB-SC-CM treatment caused a more rapid re-formation of granulation tissue and re-epithelialization of wounds, which indicates that the therapeutic effect of hCB-SC-CM is due to secreted stem cell-recruiting factors from stem cells, not just from endothelial lineage cells. Taken together, these results suggest that secretory factors released from stem cells, not just from endothelial cells, could be an important mediator of stem cell therapy in ischemic tissue diseases.

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References

  • Branski L. K.; Gauglitz G. G.; Herndon D. N.; Jeschke M. G. A review of gene and stem cell therapy in cutaneous wound healing. Burns 35: 171–180; 2009.

    Article  PubMed Central  PubMed  Google Scholar 

  • Cha J.; Falanga V. Stem cells in cutaneous wound healing. Clin. Dermatol. 25: 73–78; 2007.

    Article  PubMed  Google Scholar 

  • Cho S. W.; Moon S. H.; Lee S. H. et al. Improvement of postnatal neovascularization by human embryonic stem cell derived endothelial-like cell transplantation in a mouse model of hindlimb ischemia. Circulation 116: 2409–2419; 2007.

    Article  CAS  PubMed  Google Scholar 

  • Diegelmann R. F.; Evans M. C. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9: 283–289; 2004.

    Article  CAS  PubMed  Google Scholar 

  • Fathke C.; Wilson L.; Hutter J. et al. Contribution of bone marrow-derived cells to skin: collagen deposition and wound repair. Stem Cells 22: 812–822; 2004.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ferreira L. S.; Gerecht S.; Fuller J.; Shieh H. F.; Vunjak-Novakovic G.; Langer R. Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells. Biomaterials 28: 2706–2717; 2007.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim W. S.; Park B. S.; Sung J. H. The wound-healing and antioxidant effects of adipose-derived stem cells. Expert Opin. Biol. Ther. 9: 879–887; 2009.

    Article  CAS  PubMed  Google Scholar 

  • Kim W. S.; Park B. S.; Sung J. H. et al. 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.

    Google Scholar 

  • Levenberg S.; Zoldan J.; Basevitch Y.; Langer R. Endothelial potential of human embryonic stem cells. Blood 110: 806–814; 2007.

    Article  CAS  PubMed  Google Scholar 

  • Levenberg S. G. J.; Amit M.; Itskovitz-Eldor J.; Langer R. Endothelial cells derived from human embryonic stem cells. Proc. Natl. Acad. Sci. U. S. A. 99: 4391–4396; 2002.

    Google Scholar 

  • Li H.; Fu X.; Ouyang Y.; Cai C.; Wang J.; Sun T. Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages. Cell Tissue Res. 326: 725–736; 2006.

    Article  CAS  PubMed  Google Scholar 

  • Li W. W.; Jaffe M.; Tsakayannis D.; Li V. W. Lessons to be learned from clinical trials of angiogenesis modulators in ischemic diseases. In: Rubanyi G. (ed) Angiogenesis in health and disease. M. Dekker, Inc., NY; 1999.

  • McFarlin K.; Gao X.; Liu Y. B. et al. Bone marrow-derived mesenchymal stromal cells accelerate wound healing in the rat. Wound Repair Regen. 14: 471–478; 2006.

    Article  PubMed  Google Scholar 

  • Monaco J. L.; Lawrence W. T. Acute wound healing an overview. Clin. Plast. Surg. 30: 1–12; 2003.

    Article  PubMed  Google Scholar 

  • Ono I.; Gunji H.; Zhang J. Z.; Maruyama K.; Kaneko F. Studies on cytokines related to wound healing in donor site wound fluid. J. Dermatol. Sci. 10: 241–245; 1995.

    Article  CAS  PubMed  Google Scholar 

  • Sen C. K. Wound healing essentials: let there be oxygen. Wound Repair Regen. 17: 1–18; 2009.

    Article  PubMed Central  PubMed  Google Scholar 

  • Suh W.; Kim K. L.; Kim J. M. et al. Transplantation of endothelial progenitor cells accelerates dermal wound healing with increased recruitment of monocytes/macrophages and neovascularization. Stem Cells 23: 1571–1578; 2005.

    Article  PubMed  Google Scholar 

  • Templin C.; Grote K.; Schledzewski K. et al. Ex vivo expanded haematopoietic progenitor cells improve dermal wound healing by paracrine mechanisms. Exp. Dermatol. 18: 445–453; 2009.

    Article  CAS  PubMed  Google Scholar 

  • Urbich C.; Aicher A.; Heeschen C. et al. Soluble factors released by endothelial progenitor cells promote migration of endothelial cells and cardiac resident progenitor cells. J. Mol. Cell. Cardiol. 39: 733–742; 2005.

    Article  CAS  PubMed  Google Scholar 

  • Velazquez O. C. Angiogenesis and vasculogenesis: inducing the growth of new blood vessels and wound healing by stimulation of bone marrow-derived progenitor cell mobilization and homing. J. Vasc. Surg. 45(Suppl A): A39–A47; 2007.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wu Y.; Wang J.; Scott P. G.; Tredget E. E. Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen. 15(Suppl 1): S18–S26; 2007.

    Article  PubMed  Google Scholar 

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Acknowledgments

This research was supported by the Agenda Program (No.PJ00932102) from Rural Development Administration, Republic of Korea.

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Authors and Affiliations

  1. CHA Bio & Diostech Co., Ltd., 606-16 Yeoksam 1 dong, Gangnam gu, Seoul, 135-907, South Korea

    Jumi Kim, Ji Hye Lee & Hyung Min Chung

  2. Graduate School of Life Science, CHA Stem Cell Institute, College of Medicine, CHA University, 605-21 Yeoksam 1 dong, Gangnam gu, Seoul, 135-907, South Korea

    Su Min Yeo & Hyung Min Chung

  3. Department of Oral Pharmacology, School of Dentistry, Brain Korea 21 Plus Project, Chonbuk National University, Jeonju, 561-756, South Korea

    Jung-Il Chae

Authors
  1. Jumi Kim
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  2. Ji Hye Lee
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  3. Su Min Yeo
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  4. Hyung Min Chung
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  5. Jung-Il Chae
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Corresponding authors

Correspondence to Hyung Min Chung or Jung-Il Chae.

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Editor: T. Okamoto

Jumi Kim and Ji Hye Lee contributed equally to this work.

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Supplementary Fig. 1

Quantification analysis of c-kit positive cells in wound site after treatment of control-, hCB-SC and HUVEC conditioned medium at day 5. Quantification analysis result for c-kit positive cells in 10mm X 10mm tissue slide (n = 4) at day 5 after treatment of control-, hCB-SC and HUVEC conditioned medium. Statistical analysis was performed with the t-test. A value of P < 0.05 was considered statistically significant. The significance of differences was evaluated by paired two-tailed student’s t-tests (SAS version 8.0, Cary, NC, USA) (JPEG 38 kb)

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Kim, J., Lee, J.H., Yeo, S.M. et al. Stem cell recruitment factors secreted from cord blood-derived stem cells that are not secreted from mature endothelial cells enhance wound healing. In Vitro Cell.Dev.Biol.-Animal 50, 146–154 (2014). https://doi.org/10.1007/s11626-013-9687-0

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  • DOI: https://doi.org/10.1007/s11626-013-9687-0

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