There are many benefits to the introduction of iPSC-derived therapies including improved patient quality of life, decreased clinical drug attrition rates, and reduced pressure on healthcare systems. However, there is still much work to be done before these therapies can become clinically available. In this post, we will explore three challenges currently facing the widespread introduction of iPSC therapies to regenerative medicine.
Over 40% of all REPROCELL customers are concerned about the safety of iPSC therapeutics – and they are not alone. One key issue is the risk of mutation during reprogramming which can lead to tumor formation and reduced differentiation capacity. These genetic alterations – including chromosomal aberrations, copy number variations (CNVs), and single nucleotide variations (SNVs) – currently occur in 38-48% of iPSCs generated using integrative reprogramming methods.
The risk of tumor formation can be reduced by employing an integration-free reprogramming methodology. These non-integrative reprogramming methods include StemRNA™ 3rd Gen Reprogramming Technology. This RNA Reprogramming methodology carries the highest reprogramming efficiency and produces iPSCs of superior viability, pluripotency, and quality compared with other non-integrative reprogramming methods.
Figure 1. StemRNA™ 3rd Gen Reprogramming Technology. RNA Reprogramming is an efficient, footprint-free method for restoring pluripotency in adult cells.
2. Lack of automated production tools
If iPSC therapeutics are to become mainstream, this will require the development of more automated production tools. Already, bioreactor culture systems have been introduced for the rapid expansion of pluripotent stem cells, such as those provided by ABLE Biott and TreeFrog Therapeutics.
However, many more systems for the automation of stem cell reprogramming, differentiation, and analysis require development before the widescale introduction of these therapeutics will be possible. The video below shows how these semi-automated bioreactor systems allow the mass culture of induced pluripotent stem cells.
3. Difficulty in iPSC gene editing
Stem cells are notorious for their gene-editing difficulty, as it is challenging to maintain their pluripotency throughout the rounds of experimental optimization. Substantial experience in both molecular and stem cell biology is necessary to genetically modify iPSCs, and there are few companies or individuals skilled in both areas.
Figure 2. CRISPR gene editing of iPSCs requires substantial knowledge of both cell and molecular biology. By combining the stem cell expertise of REPROCELL with the gene-editing knowledge of GenAhead Bio, researchers can now access CRISPR-SNIPER gene editing of iPSC cells.