title: In vitro differentiation of human skin-derived multipotent stromal cells into putative endothelial-like cells.
abstract: BACKGROUND
  Multipotent stem cells have been successfully isolated from various tissues and are currently utilized for tissue-engineering and cell-based therapies. Among the many sources, skin has recently emerged as an attractive source for multipotent cells because of its abundance. Recent literature showed that skin stromal cells (SSCs) possess mesoderm lineage differentiation potential; however, the endothelial differentiation and angiogenic potential of SSC remains elusive. In our study, SSCs were isolated from human neonatal foreskin (hNFSSCs) and adult dermal skin (hADSSCs) using explants cultures and were compared with bone marrow (hMSC-TERT) and adipose tissue-derived mesenchymal stem cells (hADMSCs) for their potential differentiation into osteoblasts, adipocytes, and endothelial cells.
  
  
  RESULTS
  Concordant with previous studies, both MSCs and SSCs showed similar morphology, surface protein expression, and were able to differentiate into osteoblasts and adipocytes. Using an endothelial induction culture system combined with an in vitro matrigel angiogenesis assay, hNFSSCs and hADSSCs exhibited the highest tube-forming capability, which was similar to those formed by human umbilical vein endothelial cells (HUVEC), with hNFSSCs forming the most tightly packed, longest, and largest diameter tubules among the three cell types. CD146 was highly expressed on hNFSSCs and HUVEC followed by hADSSCs, and hMSC-TERT, while its expression was almost absent on hADMSCs. Similarly, higher vascular density (based on the expression of CD31, CD34, vWF, CD146 and SMA) was observed in neonatal skin, followed by adult dermal skin and adipose tissue. Thus, our preliminary data indicated a plausible relationship between vascular densities, and the expression of CD146 on multipotent cells derived from those tissues.
  
  
  CONCLUSIONS
  Our data is the first to demonstrate that human dermal skin stromal cells can be differentiated into endothelial lineage. Hence, SSCs represents a novel source of stem/stromal cells for tissue regeneration and the vascularization of engineered tissues. Moreover, the CD146 investigations suggested that the microenvironmental niche might contribute to direct stromal cells multipotency toward certain lineages, which warrants further investigation.
authors.affiliation: Department of Anatomy, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Vishnubalaji
authors.forename: Muthurangan
authors.initials: M
authors.lastname: Manikandan
authors.forename: May
authors.initials: M
authors.lastname: Al-Nbaheen
authors.forename: Balamuthu
authors.initials: B
authors.lastname: Kadalmani
authors.forename: Abdullah
authors.initials: A
authors.lastname: Aldahmash
authors.forename: Nehad M
authors.initials: NM
authors.lastname: Alajez
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D003470:Culture Media; D042783:Endothelial Cells / Q000166:cytology*; D052816:Foreskin / Q000166:cytology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D039902:Multipotent Stem Cells / Q000502:physiology*; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D044968:Regenerative Medicine; D012867:Skin / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D003470:Culture Media