Abstract
BackgroundThe human umbilical cord has been studied extensively in the past two decades. It is free of ethical dilemmas, non-tumorigenic, and less immunogenic and thus provides a significant advantage over other stem cell sources. The cord lining yields both mesenchymal and epithelial stem cells. The mesenchymal cells have been appraised at length by many researchers, which led to the current review focusing on the cord lining epithelial cells (CLECs). These cells have high proliferative capacity and their superior harvest and multiplication, using the revolutionary CellOptimaTM technology, makes them better candidates in comparison to contemporary adult stem cells. Following 30 replication cycles these cells have been observed to retain their stemness, with their phenotype and karyotype intact. However, their remarkable immunosuppressant properties, protecting self as well as co-transplanted allografts from rejection, are what truly define their transplantation potential. They have been successfully applied to many chronic conditions, using animal models, including type 1 diabetes, limbal stem cell deficiency, burn injuries, and wound healing, etc. with encouraging results.ConclusionsThis review first discusses some of the advantages afforded by CLECs over other stem cell lines and then delineates their potential use in various clinical applications. Clinical trials using CLECs are currently underway in the US in collaboration with CellResearch Corp. and their potential positive findings will help garner an FDA approval, likely leading to the eventual commercialization of this promising technology.
Highlights
The human umbilical cord has been studied extensively in the past two decades
Hematopoietic, epithelial, and mesenchymal cells have been isolated from umbilical cord blood, while both epithelial and mesenchymal cells have been collected from the Wharton’s jelly [6], amniotic fluid [7], amniotic membrane [8], and cord lining [5] using various techniques
With the significant advantages Cord lining epithelial stem cell (CLEC) possess over adult stem cells in terms of source, scale-up, and immunosuppressive properties, the former could prove to be a strong contender for transplantation therapy
Summary
This review briefly introduces the currently available therapies for various chronic conditions followed by their treatment limitations and possible avenues for subsequent cell-based therapies which can be explored for their potential clinical applications It delineates the various prospective stem cell sources examined far and makes a comparison with the CLEC-centered approach. This includes providing evidence-based implications for the future of CLECs in the treatment of ocular disorders, insulindependent diabetes, liver failure, wound regeneration, and various other conditions for which other stem cell sources have presented different limitations in their applicability. Abbreviations ABCG2: ATP-binding cassette sub-family G; BMI1: B lymphoma Mo-MLV insertion region 1 homolog; BMP4: Bone morphogenetic protein 4; CD: Cluster of differentiation; CK: Cytokine; CLEC: Cord lining epithelial stem cell; CLECmuc: Mucin-expressing cord lining epithelial cell; CLMC: Cord lining mesenchymal stem cell; CT: Computed tomography; CYP3A4: Cytochrome P450 3A4; eGFP: Enhanced green fluorescent protein; HAE: Human amniotic epithelial cells; HAM: Human amniotic membrane; HES1: Hairy and enhancer of split-1; hESC: Human embryonic stem cell; HGF: Hepatocyte growth factor; HLA: Human leukocyte antigen; HMM: Hepatic maintenance medium; HNF1B: Hepatocyte nuclear factor 1 homebox B; HNF4A: Hepatocyte nuclear factor 4 alpha; IL: Interleukin; KLF4: Krupple like factor 4; MESC: Mouse embryonic stem cell; MHC: Major histocompatibility complex; MYC: Mitomycin c; OCT-4: Octamer binding transcription factor 4; REX1: Reduced expression 1; SOX2: Sex determining region Y box 2; SSEA4: Stage-specific embryonic antigen; TNF-β1: Tumor necrosis factor beta-1; VEGF: Vascular endothelial growth factor; ZFN: Zinc finger nuclease
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