Autologous Induced Pluripotent Stem Cell–Based Cell Therapies: Promise, Progress, and Challenges

Abstract

The promise of human induced pluripotent stem cells (iPSCs) lies in their ability to serve as a starting material for autologous, or patient-specific, stem cellbased therapies. Since the first publications describing the generation of iPSCs from human tissue in 2007, a Phase I/IIa clinical trial testing an autologous iPSC-derived cell therapy has been initiated in the U.S., and several other autologous iPSC-based therapies have advanced through various stages of development. Three single-patient inhuman transplants of autologous iPSC-derived cells have taken place worldwide. None of the patients suffered serious adverse events, despite not undergoing immunosuppression. These promising outcomes support the proposed advantage of an autologous approach: a cell therapy product that can engraft without the risk of immune rejection, eliminating the need for immunosuppression and the associated side effects. Despite this advantage, there are currently more allogeneic than autologous iPSC-based cell therapy products in development due to the cost and complexity of scaling out manufacturing for each patient. In this review, we highlight recent progress toward clinical translation of autologous iPSC-based cell therapies. We also highlight technological advancements that would reduce the cost and complexity of autologous iPSC-based cell therapy production, enabling autologous iPSC-based therapies to become a more commonplace treatment modality for patients.

Current State and Issues of Regenerative Medicine for Rheumatic Diseases

“…The formation of teratomas due to the contamination of undifferentiated iPSCs, the possibility of cancerization due to genetic damage during the process of iPSC generation and cultivation, and the development of technology to obtain a sufficient amount and quality of cells for transplantation and a tissue structure suitable for transplantation are major issues for the future. As it takes several months to reprogram and differentiate somatic cells harvested from a patient to produce a cell therapy for the patient (88), optimizing this manufacturing timeline would help ensure that patients receive iPSC-based therapies in a timely manner.…”

From genome editing to blastocyst complementation: A new horizon in heart transplantation?

“… 12 , 13 , 14 , 15 However, the cost per individual patient and the time required to generate sufficient cell quantities or develop grafts for transplantation is currently seen as a prohibitive factor in the utilization of autologous iPSCs. 16 , 17 This is particularly problematic for time-sensitive clinical indications, such as ischemic cardiomyopathy. However, in conditions where the need for transplantation may be foreshadowed several years in advance, such as hypoplastic left heart syndrome, autologous iPSCs offer the prospect of tissue grafts or entire heart transplantation, without the need for lifelong immunosuppression.…”

Stem Cell–Based Therapies: What Interventional Radiologists Need to Know

“…100,101 Since the discovery, human iPSCs have been widely used as an alternative to human ESCs for developing autologous and patient-specific stem cell-based therapies without ethical considerations. 102,103 Currently, multiple ongoing clinical trials are using human iPSCs for various therapeutic strategies, including Parkinson's disease (PD), macular degeneration, retinitis pigmentosa, heart failure (HF), spinal cord injury, platelet transfusion, graft versus host disease, cartilage defect, and cancer immunotherapies. 104…”