Abstract
Background aims
Because of their self-renewal capacity, multilineage potential and immunomodulatory
properties, MSCs are an attractive tool for cell-based immunotherapy strategies. Foreskin,
considered as a biological waste material, has been shown to be a reservoir of therapeutic
cells.
Methods
MSCs were isolated from different foreskin samples, maintained under in vitro culture and defined according to the International Society for Cellular Therapy (ISCT)
criteria. We subsequently determined their main cell characteristics as well as their
immunobiological properties. The following parameters were determined: (i) morphology
and phenotype, (ii) proliferative and clonogenic potentials, (iii) tri-lineage differentiation
ability, (iv) immunological profile, (v) immunomodulatory properties and (vi) protein
and messenger RNA expression/secretion profile of immunoregulatory cytokines/factors
as well as the pattern of toll-like receptors (TLRs). By using a pro-inflammatory
cytokine cocktail, we also evaluated the influence of an inflammatory environment
on their biology.
Results
With a typical fibroblast-like morphology and an ISCT-compliant phenotype, foreskin-MSCs
(FSK-MSCs) were highly proliferative and had a great clonogenic potential. They displayed
multilineage capacities and interesting immunomodulatory properties. Of importance,
FSK-MSCs were not immunogenetic and were further able to inhibit T-cell proliferation.
We showed that several immunoregulatory cytokines and factors might be potentially
involved in FSK-MSC immunomodulation with particular attention to hepatocyte growth
factor and interleukin-11. Moreover, FSK-MSCs expressed several TLRs and were sensitive
to the inflammatory environment by properly adjusting their profile and fate.
Conclusions
Foreskin represents a new alternative source for MSCs that is compliant with ISCT
criteria. Their unique immunobiological properties allow consideration of FSK-MSCs
as a valuable tolerogenic product for cell-based immunotherapy.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to CytotherapyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Concise review: microRNA function in multipotent mesenchymal stromal cells.Stem Cells. 2014; 32: 1074-1082
- Mechanisms involved in the therapeutic properties of mesenchymal stem cells.Cytokine Growth Factor Rev. 2009; 20: 419-427
- Plasticity of mesenchymal stem cells in immunomodulation: pathological and therapeutic implications.Nat Immunol. 2014; 15: 1009-1016
- Biological properties of mesenchymal stem cells from different sources.Muscles Ligaments Tendons J. 2012; 2: 154-162
- Immune-related antigens, surface molecules and regulatory factors in human-derived mesenchymal stromal cells: the expression and impact of inflammatory priming.Stem Cell Rev. 2012; 8: 1188-1198
- Adipose tissue-derived stem cells and their application in bone and cartilage tissue engineering.Tissue Eng Part B Rev. 2009; 15: 113-125
- Wharton's jelly–derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications.Int J Mol Sci. 2013; 14: 11692-11712
- The therapeutic potential, challenges and future clinical directions of stem cells from the Wharton's jelly of the human umbilical cord.Stem Cell Rev. 2013; 9: 226-240
- Epidermal stem cells of the skin.Annu Rev Cell Dev Biol. 2006; 22: 339-373
- A dermal niche for multipotent adult skin-derived precursor cells.Nat Cell Biol. 2004; 6: 1082-1093
- Genetic reporter analysis reveals an expandable reservoir of OCT4+ cells in adult skin.Cell Regen (Lond). 2014; 3: 9
- Foreskins as skin grafts.Ann Surg. 1937; 106: 252-256
- Use of preputial skin for coverage of post-burn contractures of fingers in children.Indian J Plast Surg. 2011; 44: 68-71
- Propagation, expansion, and multilineage differentiation of human somatic stem cells from dermal progenitors.Stem Cells Dev. 2005; 14: 337-348
- Human dermis harbors distinct mesenchymal stromal cell subsets.J Invest Dermatol. 2012; 132: 563-574
- Human foreskin fibroblast-like stromal cells can differentiate into functional hepatocytic cells.Cell Biol Int. 2013; 37: 1308-1319
- Differentiation of human multipotent dermal fibroblasts into islet-like cell clusters.BMC Cell Biol. 2010; 11: 46
- In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells.BMC Dev Biol. 2012; 12: 7
- Mesenchymal stem cell-like cells from children foreskin inhibit the growth of SGC-7901 gastric cancer cells.Exp Mol Pathol. 2013; 94: 430-437
- Comparison of different methods for the isolation of mesenchymal stem cells from human umbilical cord Wharton's jelly.In Vitro Cell Dev Biol Anim. 2012; 48: 75-83
- Isolation of keratinocytes and fibroblasts from human foreskin by one-step enzyme incubation using liberase research grade products.Biochemica. 2009; 2: 12-14
- Proliferative and phenotypical characteristics of human adipose tissue-derived stem cells: comparison of Ficoll gradient centrifugation and red blood cell lysis buffer treatment purification methods.Cytotherapy. 2014; 16: 1220-1228
- Impact of different mesenchymal stromal cell types on T-cell activation, proliferation and migration.Int Immunopharmacol. 2013; 15: 693-702
- Environmental signals regulating mesenchymal progenitor cell growth and differentiation.in: Rajasekhar V.K. Vemuri M.C. Regulatory networks in stem cells. Humana Press, New York2009: 175-184
- Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies.FASEB J. 2003; 17: 1892-1894
- Modulated expression of adhesion molecules and galectin-1: role during mesenchymal stromal cell immunoregulatory functions.Exp Hematol. 2010; 38: 922-932
- Bone marrow mesenchymal stromal cells induce proliferative, cytokinic and molecular changes during the T cell response: the importance of the IL-10/CD210 axis.Stem Cell Rev. 2015; 11: 442-452
- Human but not murine multipotent mesenchymal stromal cells exhibit broad-spectrum antimicrobial effector function mediated by indoleamine 2,3-dioxygenase.Leukemia. 2011; 25: 648-654
- Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression.Blood. 2007; 110: 2197-2200
- IDO-independent suppression of T cell effector function by IFN-γ-licensed human mesenchymal stromal cells.J Immunol. 2014; 192: 1491-1501
- CD73 and adenosine generation in the creation of regulatory microenvironments.Clin Exp Immunol. 2013; 171: 1-7
- A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells.Blood. 2007; 110: 3691-3694
- Human mesenchymal stromal cells suppress T-cell proliferation independent of heme oxygenase-1.Cytotherapy. 2015; 17: 382-391
- Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(High) forkhead box P3+ regulatory T cells.Clin Exp Immunol. 2009; 156: 149-160
- Characterization of HLA-G and related immunosuppressive effects in human umbilical cord stroma derived stem cells.Cell Transplant. 2015; (Jun 3. [Epub ahead of print])
- Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes.Immunol Lett. 2012; 146: 50-56
- Secretion of immunoregulatory cytokines by mesenchymal stem cells.World J Stem Cells. 2014; 6: 552-570
- Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis.J Immunol. 2013; 190: 2372-2380
- Mesenchymal stem cells inhibit lymphocyte proliferation by mitogens and alloantigens by different mechanisms.Exp Cell Res. 2005; 305: 33-41
- Mesenchymal stem cell-mediated T cell suppression occurs through secreted galectins.Int J Oncol. 2011; 38: 385-390
- Leukemia inhibitory factor: role in human mesenchymal stem cells mediated immunosuppression.Cell Immunol. 2008; 253: 16-22
- Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli.Blood. 2002; 99: 3838-3843
- Identification of IL-10 and TGF-beta transcripts involved in the inhibition of T-lymphocyte proliferation during cell contact with human mesenchymal stem cells.Gene Expr. 2007; 13: 217-226
- Phenotype, donor age and gender affect function of human bone marrow-derived mesenchymal stromal cells.BMC Med. 2013; 146
- More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer.J Leukoc Biol. 2010; 88: 1109-1117
- Hepatocyte growth factor (HGF) induces interleukin-11 secretion from osteoblasts: a possible role for HGF in myeloma-associated osteolytic bone disease.Blood. 1999; 94: 3883-3888
- Synergistic effects of hepatocyte growth factor on human cord blood CD34+ progenitor cells are the result of c-met receptor expression.Stem Cells. 1996; 14: 592-602
- Mesenchymal stem cell therapy and acute graft-versus-host disease: a review.Hum Cell. 2014; 27: 137-150
- Human mesenchymal stromal cells attenuate graft-versus-host disease and maintain graft-versus-leukemia activity following experimental allogeneic bone marrow transplantation.Stem Cells. 2015; 33: 601-614
- Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation.J Clin Invest. 1998; 102: 115-123
- IL-11 separates graft-versus-leukemia effects from graft-versus-host disease after bone marrow transplantation.J Clin Invest. 1999; 104: 317-325
- Effects of inflammation on stem cells: together they strive?.EMBO Rep. 2015; 16: 416-426
- The source of human mesenchymal stromal cells influences their TLR profile as well as their functional properties.Cell Immunol. 2011; 270: 207-216
Article info
Publication history
Accepted:
November 16,
2015
Received:
September 6,
2015
Identification
Copyright
© 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
