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Taking iPSCs from Bench to Bedside: Promises and Challenges

July 05 2018

Research in developmental biology is greatly accelerated by the use of induced pluripotent stem cells (iPSCs), which have opened up many new opportunities. The use of it has also eliminated some of the major barriers that embryonic stem cell (ESC) and adult stem cell (ASC) research had to face. As a research tool, working with iPSCs means less regulatory and ethical issues compared to ESCs, a potential to differentiate into more cell types than ASCs, which does not decrease with age, and an easier cultivation and harvest process. The ground-breaking iPSC development demonstrated that biological development is not an irreversible process and provides an entirely new way of looking at disease processes and means to develop effective therapies. Based on these features, iPSCs have the potential to be revolutionary in the field of stem cells and regenerative medicine.

Funding to translate iPSC research towards the clinic

With the new BHC-7 call coming up, entitled: “Regenerative medicine: from new insights to new applications”, it is time to reflect on the current state of iPSCs in the therapeutic and clinical setting. The technology already proved to be highly promising through its use in disease modelling, drug discovery and development, and early attempts at cellular therapies. While general therapeutic mechanisms primarily treat symptoms and slow down disease progression, the use of iPSCs in regenerative medicine has the capacity to reset biology and therefore actually cure diseases. Yet, to date, the clinical use of iPSCs is still extremely limited. What future promises lie ahead and what challenges remain to be faced to truly translate iPSC research towards the clinic?

Promises

Organ transplantation is currently the sole means of survival for many patients across the world, with the unfortunate associated risks of organ rejection and the great lack of sufficient donors. iPSCs may turn out to be a very reliable source of biomaterials for clinically applicable engineered tissues. Indeed, although being a relatively young field, tissue engineering has already been extremely effective in pre-clinical studies treating several disorders, including bone defects and skin lesions. Also, early signs are very promising in the cellular therapy market. iPSC treatment of disease models of e.g. Parkinson’s disease and sickle cell anaemia have shown to be successful, indicating that therapeutic iPSC approaches are feasible.

Besides cellular replacement therapies, the ultimate and almost utopian potential of iPSCs is the creation of transplantable tissues and organs on demand tailored to each specific patient. Fortunately, current developments show that this seemingly utopian solution could actually be quite viable. The development of organoids demonstrates that the growing of more complex, artificial organs, with a remarkable degree of autonomy and function, is possible. Together with 3D tissue printing and genome-editing techniques such as the CRISPR/Cas9 system, iPSCs could be manipulated and grown in a way that fit the personalised needs of patients. We believe the time is now for breakthroughs such as these, and, indeed, some of our clients share this vision.

Challenges

Several crucial hurdles prevent the safe and reliable translation of promising developments into the clinic. As iPSCs have an unlimited differentiation capacity, they pose the risk on teratoma development from residual undifferentiated cells in medicinal products. Also, the presence of residual pathogens, such as the induction factors to create iPSCs, and harmful mutations needs to be ruled out. Even in the research setting, iPSCs show variability between studies and the reprogramming process still has a low efficiency rate. It is crucial that the quality and identity of iPSCs is maintained and that long-term safety is ensured, especially in the clinical setting. Initiatives are already being undertaken to develop robust lineage-specific differentiation protocols, and large projects are set up to develop methods for large-scale creation of iPSC lines, their consistent documentation, and storage in biobanks. We believe these challenges are primarily of a technical nature and can be tackled through joint and aligned research efforts, for example by using advanced techniques in single-cell RNA sequencing and microRNAi for extensive iPSC characterisation. Additionally, the way the regenerative approach is to be developed best, also being most practicable on a large scale, needs to be explored. Either through a patient-specific, autologous, one procedure approach, i.e. taking the patient’s own cells and grow them into an organ that the patient needs. Or through the creation of allogeneic biobanks with customised reprogramming for immune compliance with the recipient, representing a more “off-the-shelf” approach.

Also, challenges such as cost-efficiency need to be overcome to ensure scalability, and with that accessibility and affordability, of regenerative applications. Further emphasising the mentioned uncertainties, the European regulatory framework concerning iPSCs is constantly being updated, posing a major hurdle especially for smaller consortia, individual labs, and SMEs. Additional attention needs to be spent on appropriate data protection measures and regulated and proper informed consent from cell donors that is in alliance with the complex regulatory landscape. We are convinced that we can get rid of the image of iPSCs as being too risky if we join forces and focus our attention on eliminating remaining barriers.

How ttopstart can support your ambitions in the iPSC field  

Are you striving for a breakthrough and innovative developments in the iPSC field that has the potential to address the unmet clinical needs of a large patient group? Then the upcoming BHC-7 call is perfectly suited for you! As setting up an efficient research strategy to tackle current challenges will largely determine the competitiveness of your proposal, we at ttopstart would be thrilled to support you. With our co-creation mindset and full cycle support service we can assist you in every stage and offer expert support in the development of smarter funding strategies, grant writing, consortium building, project management, and implementation service.

Let us together strive to successfully bring your project from bench-to-bedside! Reach out to us to find out more.

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Contact

Boaz van Driel, PhD
+31 614 842 950