Overcoming barriers to reprogramming and differentiation in nonhuman primate induced pluripotent stem cells

Area of Science:

• Stem Cell Biology
• Regenerative Medicine
• Comparative Biology
• Primate Research

Background:

• Induced pluripotent stem cells (iPS cells) from nonhuman primates (NHPs) are crucial for regenerative medicine and comparative biology.
• Autologous iPS cells could prevent transplant rejection, but reprogramming methods need adaptation for NHPs.
• Previous NHP studies primarily used young donors, potentially overlooking age-related complications in iPS cell generation and differentiation.

Purpose of the Study:

• To investigate the impact of donor age on iPS cell generation and neural differentiation potential in common marmosets (Callithrix jacchus).
• To assess potential age-related deficits in chimpanzee (Pan troglodytes) iPS cells and identify factors influencing these differences.
• To explore methods for rescuing differentiation potential in aged NHP iPS cells.

Main Methods:

• Generated iPS cells from common marmosets across a lifespan (young, middle-aged, old).
• Subjected marmoset iPS cells to directed neural differentiation and assessed potential using quantitative polymerase chain reaction.
• Generated chimpanzee iPS cells using various technologies and evaluated their differentiation potential.

Main Results:

• Marmoset iPS cells from older donors exhibited reduced neural marker induction compared to younger donors.
• A 24-hour pretreatment with 0.5% dimethyl sulfoxide rescued the neural differentiation deficits in aged marmoset iPS cells.
• Chimpanzee iPS cells showed some differentiation deficits irrespective of the reprogramming technology used, but these were also preventable with dimethyl sulfoxide pretreatment.

Conclusions:

• Donor age can impact the differentiation potential of NHP iPS cells, with older donors showing reduced neural differentiation capacity.
• Dimethyl sulfoxide pretreatment is an effective method to rescue differentiation deficits in iPS cells from aged marmosets and chimpanzees.
• These findings have implications for utilizing NHP iPS cells in regenerative medicine and comparative studies, particularly when using cells from diverse age groups.