Human induced pluripotent stem cells (hiPSCs) offer transformative potential for biomedical applications by providing an abundant source of patient-specific, pluripotent cells with fewer ethical concerns than embryonic stem cells. However, significant challenges related to safety, efficiency, and scale-up need to be addressed for their widespread clinical use. 

 Advantages of Using hiPSCs

• Patient-Specific Therapies/Reduced Immune Rejection: hiPSCs can be generated from a patient’s own somatic cells (e.g., skin or blood), which can then be differentiated into the required cell type for transplantation. This autologous approach significantly minimizes the risk of immune rejection, a major hurdle with allogeneic (donor-derived) transplants.
• Disease Modeling: hiPSCs enable the creation of “disease-in-a-dish” models using cells derived from patients with specific genetic disorders. This allows researchers to study the mechanisms of diseases, such as Parkinson’s or Alzheimer’s, in human cell types that would otherwise be inaccessible, offering more accurate insights than animal models.
• Drug Discovery and Toxicity Testing: Patient-specific or genetically-edited hiPSC-derived cells can be used as platforms to screen new drugs for safety and efficacy. This can reduce reliance on animal testing and help predict human-specific responses and potential toxicities.
• Unlimited Proliferation Potential: hiPSCs possess the ability to self-renew and proliferate indefinitely in culture, providing a theoretically unlimited supply of cells for both research and therapeutic purposes.
• Ethical Advantage: Unlike human embryonic stem cells (hESCs), the derivation of hiPSCs does not involve the destruction of an embryo, which circumvents many of the ethical concerns associated with hESCs. 

Challenges of Using hiPSCs

• Tumorigenicity Risk: A primary concern is the potential for undifferentiated hiPSCs to form tumors (teratomas) after transplantation. The reprogramming process itself, especially with the use of certain oncogenes like c-Myc in early methods, or genetic instability during prolonged culturing, can increase this risk.
• Reprogramming Inefficiency and Variability: The process of generating hiPSCs from somatic cells can be inefficient. Moreover, different iPSC lines, even from the same source, can exhibit variability in their differentiation potential and genetic stability (epigenetic memory), which complicates standardization for clinical use.
• Immunogenicity Concerns: While autologous transplants aim to eliminate rejection, studies have suggested that even patient-matched hiPSC-derived cells might elicit a minor immune response. For allogeneic “off-the-shelf” therapies, immune rejection remains a significant barrier, often requiring the use of immunosuppressant drugs.
• Cell Immaturity: hiPSC-derived cells often exhibit characteristics of embryonic or fetal cells rather than fully mature adult cells, which may limit their functionality and effectiveness in certain therapeutic applications.
• Cost and Scalability: Producing large quantities of clinical-grade hiPSC-derived cells is costly and logistically challenging, largely due to expensive growth factors, rigorous quality control measures, and complex manufacturing processes. 

 Way forward

Combining hiPSC technology with 3D culture techniques, such as organoids and 3D bioprinting, can help generate more physiologically relevant tissues and organs, improving disease modeling and the potential for regenerative medicine.