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Table 1 Comparison of umbilical cord lining epithelial cells with other contemporary stem cell sources

From: Short review on human umbilical cord lining epithelial cells and their potential clinical applications

 

ESCs

Induced pluripotent stem cells (iPSCs)

Bone marrow-derived stem cells (adult stem cells)

Umbilical cord lining epithelial stem cells

Source

• Pluripotent stem cell source

• Controversial sourcing

• Requires invasive procedure

• Pluripotent cells

• Reprogrammed adult blood or dermal fibroblast cells

• Inefficient generation procedure (0.01–1%)

• Relatively expensive autologous transplantation procedure

• Multipotent stem cells

• Derived using an invasive procedure

• Potential risks and significant discomfort to the donor

• Limited proliferative capacity

• Aging at each doubling

• Multipotent stem cells

• Source is medical waste and inexpensive

• Devoid of maternal or fetal morbidity

• Billions of cells can be isolated from the primary cell source.

• Stemness retained after 30 replication cycles with their phenotype and karyotype intact

Tumorigenicity

• Characteristically produce teratomas

• Aneuploidy and accumulation of oncogenic mutations over multiple replication cycles produce aggressive teratocarcinomas

• MYC used in cell line generation is oncogenic

• Cell line generation through viral vectors can activate integration site-adjacent oncogenes or suppress the tumor suppressor genes

• Possible precursor adult cell epigenetic memory retention

• Teratomas from undifferentiated cell contamination in the final product

• Genetically modified cells can generate teratomas through proto-oncogenic activation

• Highly proliferative but do not produce tumors

• Acquiescent to transgene integration sans tumorigenesis

Immunogenecity

In undifferentiated state:

• Low immunogenicity

• No expression of immunomodulatory molecules such as CD95 and IL-10

In differentiated state :

• Immunogenicity is similar to adult fibroblasts

• Mouse ESCs acquiescent to syngenic but not allogenic transplantations

Initially, T-cell-mediated autoimmune rejection observed in:

• iPSC-derived myocardial, endothelial cells

• Teratoma formation models

Recently, successful allogenic transplantation of iPSC derived retinal pigment epithelial cells in immune-matched monkeys observed

• Clinical study to observe iPSCs’ ability to arrest macular degeneration approved in Japan

• Long history of safety in clinical trials

• Possible immunomodulatory properties Possible applications in:

• Hematological malignancies and severe aplastic anemia

• Autoimmune disorders

• Express MHC class I molecules HLA- A, B, and C as well as the non-classic HLA-G and -E

• HLA-G and -E modulate maternal immune response, suppressing T cells, NK cells and dendritic cells

• No expression of the co-stimulatory cell surface markers

• Ideal for allogenic transplantation

• Prolong co-transplanted cell survival

  1. Abbreviations: ESC embryonic stem cell, HLA human leukocyte antigen, iPSC induced pluripotent stem cell, MHC major histocompatibility complex, NK natural killer