Endothelium Trans Differentiated from Wharton's Jelly Mesenchymal Cells Promote Tissue Regeneration: Potential Role of Soluble Pro-angiogenic Factors

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Nov 21

PMID 25412260

Citations 16

Authors

Valeria Aguilera

Luis Briceno

Hector Contreras

Liliana Lamperti

Esperanza Sepulveda

Francisca Diaz-Perez

Marcelo Leon

Carlos Veas

Rafael Maura

Jorge Roberto Toledo

Paulina Fernandez

Ambart Covarrubias

Felipe Andres Zuniga

Claudia Radojkovic

Carlos Escudero

Claudio Aguayo

Affiliations

Soon will be listed here.

Abstract

Background: Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo.

Methods: Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO).

Results: hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures.

Conclusion: These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

Citing Articles

Immune-privileged cord blood-derived endothelial colony-forming cells: advancing immunomodulation and vascular regeneration.

Smadja D, Berkane Y, Bentounes N, Rancic J, Cras A, Pinault C Angiogenesis. 2025; 28(2):19.

PMID: 40047974 PMC: 11885380. DOI: 10.1007/s10456-025-09973-9.

The GPI-Anchored Protein Thy-1/CD90 Promotes Wound Healing upon Injury to the Skin by Enhancing Skin Perfusion.

Perez L, Leon J, Lopez J, Rojas D, Reyes M, Contreras P Int J Mol Sci. 2022; 23(20).

PMID: 36293394 PMC: 9603913. DOI: 10.3390/ijms232012539.

Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet.

Reyes C, Nova-Lamperti E, Duran-Sandoval D, Rojas D, Gajardo J, Guzman-Gutierrez E Int J Mol Sci. 2022; 23(13).

PMID: 35806336 PMC: 9266330. DOI: 10.3390/ijms23137329.

Mesenchymal Stem Cells Regenerate Diabetic Foot Ulcers: A Review Article.

Verdi J, Shirian S, Saleh M, Haghighian H, Kavianpour M World J Plast Surg. 2022; 11(1):12-22.

PMID: 35592239 PMC: 9018029. DOI: 10.52547/wjps.11.1.12.

Secretome from Human Mesenchymal Stem Cells-Derived Endothelial Cells Promotes Wound Healing in a Type-2 Diabetes Mouse Model.

Ormazabal V, Nova-Lampeti E, Rojas D, A Zuniga F, Escudero C, Lagos P Int J Mol Sci. 2022; 23(2).

PMID: 35055129 PMC: 8779848. DOI: 10.3390/ijms23020941.

References

Kim S, Zhang H, Kim C, Kim J, Kim M . Amniotic mesenchymal stem cells with robust chemotactic properties are effective in the treatment of a myocardial infarction model. Int J Cardiol. 2012; 168(2):1062-9. DOI: 10.1016/j.ijcard.2012.11.003. View

Weiss M, Medicetty S, Bledsoe A, Rachakatla R, Choi M, Merchav S . Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells. 2005; 24(3):781-92. DOI: 10.1634/stemcells.2005-0330. View

Li Z, Guo J, Chang Q, Zhang A . Paracrine role for mesenchymal stem cells in acute myocardial infarction. Biol Pharm Bull. 2009; 32(8):1343-6. DOI: 10.1248/bpb.32.1343. View

Diaz-Perez F, Radojkovic C, Aguilera V, Veas C, Gonzalez M, Lamperti L . L-arginine transport and nitric oxide synthesis in human endothelial progenitor cells. J Cardiovasc Pharmacol. 2012; 60(5):439-49. DOI: 10.1097/FJC.0b013e318269ae2f.. View

Wang H, Hung S, Peng S, Huang C, Wei H, Guo Y . Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells. 2004; 22(7):1330-7. DOI: 10.1634/stemcells.2004-0013. View

Rachakatla R, Marini F, Weiss M, Tamura M, Troyer D . Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors. Cancer Gene Ther. 2007; 14(10):828-35. DOI: 10.1038/sj.cgt.7701077. View

Liu J, Dunoyer-Geindre S, Serre-Beinier V, Mai G, Lambert J, Fish R . Characterization of endothelial-like cells derived from human mesenchymal stem cells. J Thromb Haemost. 2007; 5(4):826-34. DOI: 10.1111/j.1538-7836.2007.02381.x. View

Tang Y, Zhao Q, Zhang Y, Cheng L, Liu M, Shi J . Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul Pept. 2003; 117(1):3-10. DOI: 10.1016/j.regpep.2003.09.005. View

Miranville A, Heeschen C, Sengenes C, Curat C, Busse R, Bouloumie A . Improvement of postnatal neovascularization by human adipose tissue-derived stem cells. Circulation. 2004; 110(3):349-55. DOI: 10.1161/01.CIR.0000135466.16823.D0. View

10.

Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A . Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med. 2004; 351(22):2276-85. DOI: 10.1056/NEJMoa041469. View

11.

Kim S, Zhang H, Guo L, Kim J, Kim M . Amniotic mesenchymal stem cells enhance wound healing in diabetic NOD/SCID mice through high angiogenic and engraftment capabilities. PLoS One. 2012; 7(7):e41105. PMC: 3398889. DOI: 10.1371/journal.pone.0041105. View

12.

Liu Y, Wu J, Zhu Y, Han J . Therapeutic application of mesenchymal stem cells in bone and joint diseases. Clin Exp Med. 2012; 14(1):13-24. DOI: 10.1007/s10238-012-0218-1. View

13.

Stenderup K, Justesen J, Clausen C, Kassem M . Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone. 2003; 33(6):919-26. DOI: 10.1016/j.bone.2003.07.005. View

14.

Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M . Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis. Arterioscler Thromb Vasc Biol. 2008; 29(1):61-6. DOI: 10.1161/ATVBAHA.108.166496. View

15.

Chen L, Tredget E, Wu P, Wu Y . Paracrine factors of mesenchymal stem cells recruit macrophages and endothelial lineage cells and enhance wound healing. PLoS One. 2008; 3(4):e1886. PMC: 2270908. DOI: 10.1371/journal.pone.0001886. View

16.

Mitchell K, Weiss M, Mitchell B, Martin P, Davis D, Morales L . Matrix cells from Wharton's jelly form neurons and glia. Stem Cells. 2003; 21(1):50-60. DOI: 10.1634/stemcells.21-1-50. View

17.

Lu L, Liu Y, Yang S, Zhao Q, Wang X, Gong W . Isolation and characterization of human umbilical cord mesenchymal stem cells with hematopoiesis-supportive function and other potentials. Haematologica. 2006; 91(8):1017-26. View

18.

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. 2006; 326(3):725-36. DOI: 10.1007/s00441-006-0270-9. View

19.

Fernandez P, Jara C, Aguilera V, Caviedes L, Diaz F, Radojkovic C . Adenosine A₂A and A₃ receptors are involved in the human endothelial progenitor cells migration. J Cardiovasc Pharmacol. 2012; 59(5):397-404. DOI: 10.1097/FJC.0b013e3182471d14. View

20.

Tang J, Wang J, Yang J, Kong X, Zheng F, Guo L . Mesenchymal stem cells over-expressing SDF-1 promote angiogenesis and improve heart function in experimental myocardial infarction in rats. Eur J Cardiothorac Surg. 2009; 36(4):644-50. DOI: 10.1016/j.ejcts.2009.04.052. View