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Home / Equine Research Bank / Stem Cell Res Ther / Microencapsulated equine mesenchymal stromal cells promote c...
Stem cell research & therapy2015; 6(1); 66; doi: 10.1186/s13287-015-0037-x

Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro.

Abstract: The prevalence of impaired cutaneous wound healing is high and treatment is difficult and often ineffective, leading to negative social and economic impacts for our society. Innovative treatments to improve cutaneous wound healing by promoting complete tissue regeneration are therefore urgently needed. Mesenchymal stromal cells (MSCs) have been reported to provide paracrine signals that promote wound healing, but (i) how they exert their effects on target cells is unclear and (ii) a suitable delivery system to supply these MSC-derived secreted factors in a controlled and safe way is unavailable. The present study was designed to provide answers to these questions by using the horse as a translational model. Specifically, we aimed to (i) evaluate the in vitro effects of equine MSC-derived conditioned medium (CM), containing all factors secreted by MSCs, on equine dermal fibroblasts, a cell type critical for successful wound healing, and (ii) explore the potential of microencapsulated equine MSCs to deliver CM to wounded cells in vitro. Methods: MSCs were isolated from the peripheral blood of healthy horses. Equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line were wounded in vitro, and cell migration and expression levels of genes involved in wound healing were evaluated after treatment with MSC-CM or NBL-6-CM. These assays were repeated by using the CM collected from MSCs encapsulated in core-shell hydrogel microcapsules. Results: Our salient findings were that equine MSC-derived CM stimulated the migration of equine dermal fibroblasts and increased their expression level of genes that positively contribute to wound healing. In addition, we found that equine MSCs packaged in core-shell hydrogel microcapsules had similar effects on equine dermal fibroblast migration and gene expression, indicating that microencapsulation of MSCs does not interfere with the release of bioactive factors. Conclusions: Our results demonstrate that the use of CM from MSCs might be a promising new therapy for impaired cutaneous wounds and that encapsulation may be a suitable way to effectively deliver CM to wounded cells in vivo.
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Publication Date: 2015-04-11 PubMed ID: 25889766PubMed Central: PMC4413990DOI: 10.1186/s13287-015-0037-xGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research is about how microencapsulated mesenchymal stromal cells (MSCs) derived from horses can promote wound healing, examining the effects of microencapsulated MSCs on equine dermal fibroblasts, and exploring an effective delivery system for these cells.

Understanding the Research

  • The study is based on the high prevalence of impaired cutaneous (skin) wound healing. Current treatments are often ineffective and can lead to negative social and economic impacts.
  • The existing hole in our knowledge regarding wound healing are two-fold; first, how mesenchymal stromal cells (MSCs) exert their effects on the cells they target is not fully understood. Secondly, there is no known effective and safe delivery system to supply these MSC-derived factors to their target cells.
  • This research aims to better understand the role of MSCs in wound healing. It uses equine MSC-derived conditioned medium (CM), a nutrient-rich liquid in which cells have been fragmented and contains all the factors secreted by MSCs, to study how these cells influence equine dermal fibroblasts, which play a crucial role in wound healing.
  • The researchers also explore microencapsulation, a potential method for delivering MSCs to wound cells. Mesenchymal stromal cells are encapsulated in small, biologically inert particles, sort of medical ‘microcapsules’.

Methods and Findings

  • The researchers extracted MSCs from the peripheral blood of healthy horses. They wounded equine dermal fibroblasts from the NBL-6 (horse dermal fibroblast cell) line in vitro and evaluated their migration and gene expression levels after treatment with MSC-derived conditioned medium or NBL-6 derived conditioned medium.
  • Post-treatment, they observed the effects of the conditioned medium collected from microencapsulated MSCs on the wounded fibroblasts.
  • Results marked a considerable increase in fibroblast migration and gene expression linked with wound healing after the treatment with MSC-derived conditioned medium. They also found that encapsulated MSCs had similar effects, indicating that the process did not hinder the release of bioactive factors.

Conclusions

  • The study concludes that the conditioned medium derived from MSCs can potentially offer an effective new therapy for impaired skin wounds.
  • Additionally, encapsulation could serve as an efficient method to deliver this medium to the wounded cells in vivo, enabling a more targeted therapeutic approach.

Cite This Article

APA
Bussche L, Harman RM, Syracuse BA, Plante EL, Lu YC, Curtis TM, Ma M, Van de Walle GR. (2015). Microencapsulated equine mesenchymal stromal cells promote cutaneous wound healing in vitro. Stem Cell Res Ther, 6(1), 66. https://doi.org/10.1186/s13287-015-0037-x

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 6
Issue: 1
Pages: 66

Researcher Affiliations

Bussche, Leen
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. lb548@cornell.edu.
Harman, Rebecca M
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. rmh12@cornell.edu.
Syracuse, Bethany A
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. bas346@cornell.edu.
Plante, Eric L
  • Department of Biological Sciences, State University of New York at Cortland, 21 Graham Avenue, Cortland, NY, 13045, USA. eric.plante@cortland.edu.
Lu, Yen-Chun
  • Department of Biological and Environmental Engineering, Cornell University, Wing Road, Ithaca, NY, 14850, USA. yl2347@cornell.edu.
Curtis, Theresa M
  • Department of Biological Sciences, State University of New York at Cortland, 21 Graham Avenue, Cortland, NY, 13045, USA. theresa.curtis@cortland.edu.
Ma, Minglin
  • Department of Biological and Environmental Engineering, Cornell University, Wing Road, Ithaca, NY, 14850, USA. mm826@cornell.edu.
Van de Walle, Gerlinde R
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, 235 Hungerford Hill Road, Ithaca, NY, 14850, USA. grv23@cornell.edu.

MeSH Terms

  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy / methods
  • Chemokine CXCL10 / biosynthesis
  • Cobalt / pharmacology
  • Culture Media, Conditioned / pharmacology
  • Female
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Guided Tissue Regeneration / methods
  • Horses
  • Interferon-gamma / pharmacology
  • Interleukin-8 / biosynthesis
  • Matrix Metalloproteinase 1 / biosynthesis
  • Matrix Metalloproteinase 13 / biosynthesis
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / physiology
  • Mitomycin / pharmacology
  • Models, Animal
  • Skin / injuries
  • Skin Diseases / therapy
  • Tumor Necrosis Factor-alpha / pharmacology
  • Wound Healing / drug effects
  • Wound Healing / physiology

References

This article includes 48 references
  1. Van den Broek LJ, Limandjaja GC, Niessen FB, Gibbs S. Human hypertrophic and keloid scar models: principles, limitations and future challenges from a tissue engineering perspective.. Exp Dermatol 2014;23:382–6.
    doi: 10.1111/exd.12419pmc: PMC4369123pubmed: 24750541google scholar: lookup
  2. Clark JA, Leung KS, Cheng JC, Leung PC. The hypertrophic scar and microcirculation properties.. Burns 1996;22:447–50.
    doi: 10.1016/0305-4179(95)00166-2pubmed: 8884003google scholar: lookup
  3. Jackson WM, Nesti LJ, Tuan RS. Concise review: clinical translation of wound healing therapies based on mesenchymal stem cells.. Stem Cells Transl Med 2012;1:44–50.
    doi: 10.5966/sctm.2011-0024pmc: PMC3727688pubmed: 23197639google scholar: lookup
  4. Morris DE, Wu L, Zhao LL, Bolton L, Roth SI, Ladin DA. Acute and chronic animal models for excessive dermal scarring: quantitative studies.. Plast Reconstr Surg 1997;100:674–81.
    doi: 10.1097/00006534-199709000-00021pubmed: 9283567google scholar: lookup
  5. Aksoy MH, Vargel I, Canter IH, Erk Y, Sargon M, Pinar A. A new experimental hypertrophic scar model in guinea pigs.. Aesthet Plast Surg 2002;26:388–96.
    doi: 10.1007/s00266-002-1121-zpubmed: 12432481google scholar: lookup
  6. Dorsett-Martin WA. Rat models of skin wound healing: a review.. Wound Repair Regen 2004;12:591–9.
    doi: 10.1111/j.1067-1927.2004.12601.xpubmed: 15555049google scholar: lookup
  7. Theoret CL, Wilmink JM. Aberrant wound healing in the horse: naturally occurring conditions reminiscent of those observed in man.. Wound Repair Regen 2013;21:365–71.
    doi: 10.1111/wrr.12018pubmed: 23441750google scholar: lookup
  8. Theoret CL, Olutoye OO, Parnell LKS, Hicks J. Equine exuberant granulation tissue and human keloids: a comparative histopathologic study.. Vet Surg 2013;42:783–9.
    pubmed: 24015864
  9. Dittmer J, Leyh B. Paracrine effects of stem cells in wound healing and cancer progression (Review). Int J Oncol 2014;44:1789–98.
    pmc: PMC4063537pubmed: 24728412
  10. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses.. Blood 2005;105:1815–22.
    doi: 10.1182/blood-2004-04-1559pubmed: 15494428google scholar: lookup
  11. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy.. Circ Res 2008;103:1204–19.
    doi: 10.1161/CIRCRESAHA.108.176826pmc: PMC2667788pubmed: 19028920google scholar: lookup
  12. Ono I, Yamashita T, Hida T, Jin HY, Ito Y, Hamada H. Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds.. J Surg Res 2004;120:47–55.
    doi: 10.1016/j.jss.2003.08.242pubmed: 15172189google scholar: lookup
  13. Baglio SR, Pegtel DM, Baldini N. Mesenchymal stem cell secreted vesicles provide novel opportunities in (stem) cell-free therapy.. Front Physiol 2012;3:359.
    doi: 10.3389/fphys.2012.00359pmc: PMC3434369pubmed: 22973239google scholar: lookup
  14. Madrigal M, Rao KS, Riordan NH. A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods.. J Transl Med 2014;12:260.
    doi: 10.1186/s12967-014-0260-8pmc: PMC4197270pubmed: 25304688google scholar: lookup
  15. Bussche L, Van de Walle GR. Peripheral blood-derived mesenchymal stromal cells promote angiogenesis via paracrine stimulation of vascular endothelial growth factor secretion in the equine model.. Stem Cells Transl Med 2014;3:1514–25.
    doi: 10.5966/sctm.2014-0138pmc: PMC4250216pubmed: 25313202google scholar: lookup
  16. Haarer J, Johnson CL, Soeder Y, Dahlke MH. Caveats of mesenchymal stem cell therapy in solid organ transplantation.. Transpl Int 2015;28:1–9.
    doi: 10.1111/tri.12415pubmed: 25082213google scholar: lookup
  17. Maguire G. Stem cell therapy without the cells.. Commun Integr Biol 2013;6:e26631.
    doi: 10.4161/cib.26631pmc: PMC3925653pubmed: 24567776google scholar: lookup
  18. Chen CP, Chen YY, Huang JP, Wu YH. The effect of conditioned medium derived from human placental multipotent mesenchymal stromal cells on neutrophils: possible implications for placental infection.. Mol Hum Reprod 2014;20:1117–25.
    doi: 10.1093/molehr/gau062pubmed: 25140001google scholar: lookup
  19. Akram KM, Samad S, Spiteri MA, Forsyth NR. Mesenchymal stem cells promote alveolar epithelial cell wound repair in vitro through distinct migratory and paracrine mechanisms.. Respir Res 2013;14:9.
    doi: 10.1186/1465-9921-14-9pmc: PMC3598763pubmed: 23350749google scholar: lookup
  20. Chang TMS. Therapeutic applications of polymeric artificial cells.. Nat Rev Drug Discov 2005;4:221–35.
    doi: 10.1038/nrd1659pubmed: 15738978google scholar: lookup
  21. Orive G, Santos E, Pedraz JL, Hernández RM. Application of cell encapsulation for controlled delivery of biological therapeutics.. Adv Drug Deliv Rev 2014;67–68:3–14.
    doi: 10.1016/j.addr.2013.07.009pubmed: 23886766google scholar: lookup
  22. Xu K, Cantu DA, Fu Y, Kim J, Zheng X, Hematti P. Thiol-ene Michael-type formation of gelatin/poly(ethylene glycol) biomatrices for three-dimensional mesenchymal stromal/stem cell administration to cutaneous wounds.. Acta Biomater 2013;9:8802–14.
    doi: 10.1016/j.actbio.2013.06.021pmc: PMC3791182pubmed: 23811217google scholar: lookup
  23. Spaas JH, De Schauwer C, Cornillie P, Meyer E, Van Soom A, Van de Walle GR. Culture and characterisation of equine peripheral blood mesenchymal stromal cells.. Vet J 2013;195:107–13.
    doi: 10.1016/j.tvjl.2012.05.006pubmed: 22717781google scholar: lookup
  24. Lu Y, Song W, An D, Kim BJ, Schwartz R, Wu M. Designing compartmentalized hydrogel microparticles for cell encapsulation and scalable 3D cell culture.. J Mater Chem B 2015;3:353–60.
    doi: 10.1039/C4TB01735Hpubmed: 32262039google scholar: lookup
  25. Image J. http://imagej.nih.gov/ij/. Accessed 8 November 2014.
  26. Keese CR, Wegener J, Walker SR, Giaever I. Electrical wound-healing assay for cells in vitro.. Proc Natl Acad Sci U S A 2004;101:1554–9.
    doi: 10.1073/pnas.0307588100pmc: PMC341773pubmed: 14747654google scholar: lookup
  27. De Schauwer C, Gossens K, Piepers S, Hoogewijs MK, Govaere JLJ, Smits K. Characterization and profiling of immunomodulatory genes of equine mesenchymal stromal cells from non-invasive sources.. Stem Cell Res Ther 2014;5:6.
    doi: 10.1186/scrt395pmc: PMC4055120pubmed: 24418262google scholar: lookup
  28. Doubling Time. http://www.doubling-time.com/compute.php. Accessed 6 November 2014.
  29. Spiekstra SW, Breetveld M, Rustemeyer T, Scheper RJ, Gibbs S. Wound-healing factors secreted by epidermal keratinocytes and dermal fibroblasts in skin substitutes.. Wound Repair Regen 2007;15:708–17.
    doi: 10.1111/j.1524-475X.2007.00280.xpubmed: 17971017google scholar: lookup
  30. Fronza M, Heinzmann B, Hamburger M, Laufer S, Merfort I. Determination of the wound healing effect of Calendula extracts using the scratch assay with 3T3 fibroblasts.. J Ethnopharmacol 2009;126:463–7.
    doi: 10.1016/j.jep.2009.09.014pubmed: 19781615google scholar: lookup
  31. Wu NL, Chiang YC, Huang CC, Fang JY, Chen DF, Hung CF. Zeaxanthin inhibits PDGF-BB-induced migration in human dermal fibroblasts.. Exp Dermatol 2010;19:e173–81.
    doi: 10.1111/j.1600-0625.2009.01036.xpubmed: 20482615google scholar: lookup
  32. Heo SC, Jeon ES, Lee IH, Kim HS, Kim MB, Kim JH. Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms.. J Invest Dermatol 2011;131:1559–67.
    doi: 10.1038/jid.2011.64pubmed: 21451545google scholar: lookup
  33. Lee TJ, Jang J, Kang S, Bhang SH, Jeong GJ, Shin H. Mesenchymal stem cell-conditioned medium enhances osteogenic and chondrogenic differentiation of human embryonic stem cells and human induced pluripotent stem cells by mesodermal lineage induction.. Tissue Eng Part A 2014;20:1306–13.
    doi: 10.1089/ten.tea.2013.0265pmc: PMC3993069pubmed: 24224833google scholar: lookup
  34. Chen L, Xu Y, Zhao J, Zhang Z, Yang R, Xie J. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice.. PLoS One 2014;9:e96161.
    doi: 10.1371/journal.pone.0096161pmc: PMC4004560pubmed: 24781370google scholar: lookup
  35. Jun EK, Zhang Q, Yoon BS, Moon JH, Lee G, Park G. Hypoxic conditioned medium from human amniotic fluid-derived mesenchymal stem cells accelerates skin wound healing through TGF-β/SMAD2 and PI3K/Akt pathways.. Int J Mol Sci 2014;15:605–28.
    doi: 10.3390/ijms15010605pmc: PMC3907828pubmed: 24398984google scholar: lookup
  36. De Schauwer C, Piepers S, Van de Walle GR, Denmeyere K, Hoogewijs MK, Govaere JLJ. In search for cross-reactivity to immunophenotype equine mesenchymal stromal cells by multicolor flow cytometry.. Cytometry A 2012;81:312–23.
    doi: 10.1002/cyto.a.22026pubmed: 22411893google scholar: lookup
  37. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini FC, Krause DS. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.. Cytotherapy 2006;8:315–7.
    doi: 10.1080/14653240600855905pubmed: 16923606google scholar: lookup
  38. Stevens LJ, Page-McCaw A. A secreted MMP is required for reepithelialization during wound healing.. Mol Biol Cell 2012;23:1068–79.
    doi: 10.1091/mbc.E11-09-0745pmc: PMC3302734pubmed: 22262460google scholar: lookup
  39. Woessner JF. Matrix metalloproteinases and their inhibitors in connective tissue remodeling.. FASEB J 1991;5:2145–54.
    pubmed: 1850705
  40. Gillitzer R, Goebeler M. Chemokines in cutaneous wound healing.. J Leukoc Biol 2001;69:513–21.
    pubmed: 11310836
  41. Luster MI. Inflammation, tumor necrosis factor, and toxicology.. Environ Health Perspect 1998;106:A418–9.
    pmc: PMC1533145pubmed: 9841206
  42. Siddappa R, Licht R, van Blitterswijk C, de Boer J. Donor variation and loss of multipotency during in vitro expansion of human mesenchymal stem cells for bone tissue engineering.. J Orthop Res 2007;25:1029–41.
    doi: 10.1002/jor.20402pubmed: 17469183google scholar: lookup
  43. Siegel G, Kluba T, Hermanutz-Klein U, Bieback K, Northoff H, Schafer R. Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells.. BMC Med 2013;11:146.
    doi: 10.1186/1741-7015-11-146pmc: PMC3694028pubmed: 23758701google scholar: lookup
  44. Barminko J, Kim JH, Otsuka S, Gray A, Schloss R, Grumet M. Encapsulated mesenchymal stromal cells for in vivo transplantation.. Biotechnol Bioeng 2011;108:2747–58.
    doi: 10.1002/bit.23233pmc: PMC3178737pubmed: 21656712google scholar: lookup
  45. Alunno A, Montanucci P, Bistoni O, Basta G, Caterbi S, Pescara T. In vitro immunomodulatory effects of microencapsulated umbilical cord Wharton jelly-derived mesenchymal stem cells in primary Sjogren’s syndrome.. Rheumatology 2015;54:163–8.
    doi: 10.1093/rheumatology/keu292pubmed: 25065014google scholar: lookup
  46. Attia N, Santos E, Abdelmouty H, Arafa S, Zohdy N, Hernandez RM. Behaviour and ultrastructure of human bone marrow-derived mesenchymal stem cells immobilised in alginate-poly- l -lysine-alginate microcapsules.. J Microencapsul 2014;31:579–89.
    doi: 10.3109/02652048.2014.898706pubmed: 24766209google scholar: lookup
  47. Vecchiatini R, Penolazzi L, Lambertini E, Angelozzzi M, Morganit C, Mazzitelli S. Effect of dynamic three-dimensional culture on osteogenic potential of human periodontal ligament-derived mesenchymal stem cells entrapped in alginate microbeads.. J Periodontal Res 2014.
    pubmed: 25251713doi: 10.1111/jre.12225google scholar: lookup
  48. Theoret CL, Barber SM, Moyana TN, Gordon JR. Preliminary observations on expression of transforming growth factors beta1 and beta3 in equine full-thickness skin wounds healing normally or with exuberant granulation tissue.. Vet Surg 2002;31:266–73.
    doi: 10.1053/jvet.2002.32394pubmed: 11994855google scholar: lookup
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