Harnessing the Power of Induced Pluripotent Stem Cells and Gene Editing Technology: Therapeutic Implications in Hematological Malignancies

Abstract

In vitro modeling of hematological malignancies not only provides insights into the influence of genetic aberrations on cellular and molecular mechanisms involved in disease progression but also aids development and evaluation of therapeutic agents. Owing to their self-renewal and differentiation capacity, induced pluripotent stem cells (iPSCs) have emerged as a potential source of short in supply disease-specific human cells of the hematopoietic lineage. Patient-derived iPSCs can recapitulate the disease severity and spectrum of prognosis dictated by the genetic variation among patients and can be used for drug screening and studying clonal evolution. However, this approach lacks the ability to model the early phases of the disease leading to cancer. The advent of genetic editing technology has promoted the generation of precise isogenic iPSC disease models to address questions regarding the underlying genetic mechanism of disease initiation and progression. In this review, we discuss the use of iPSC disease modeling in hematological diseases, where there is lack of patient sample availability and/or difficulty of engraftment to generate animal models. Furthermore, we describe the power of combining iPSC and precise gene editing to elucidate the underlying mechanism of initiation and progression of various hematological malignancies. Finally, we discuss the power of iPSC disease modeling in developing and testing novel therapies in a high throughput setting.

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

“…iPSCs, on the other hand, can be reprogrammed from somatic cells obtained from healthy individuals, allowing researchers to study the early stages of carcinogenesis [ 554 ]. This provides a unique opportunity to uncover the molecular changes and cellular processes that drive cancer initiation, offering insights into early detection and prevention strategies [ 555 ]. Furthermore, iPSCs offer a powerful tool for drug screening and personalized therapy development.…”

“…Through high-throughput screening approaches, large libraries of compounds can be screened against iPSC-derived cancer cells, leading to the identification of novel drug candidates and personalized treatment options [ 548 , 586 ]. Immunotherapies, which harness the body’s immune system to target and eliminate cancer cells, have revolutionized cancer treatment in recent years [ 555 , 587 ]. iPSCs hold great promise in this field as well, as they can be engineered to express tumor-specific antigens and used as a source for generating patient-specific immune cells.…”

“…iPSCs have the potential to advance precision medicine by providing patient-specific models for personalized therapies and enabling the identification of specific genetic and epigenetic alterations associated with cancer [ 576 ]. The development of new cancer therapies is also within reach, as iPSCs can be utilized for drug screening, gene therapy, and the production of immune cells with enhanced anti-tumor properties [ 551 , 555 , 584 , 596 ]. However, further advancements are needed in the development of more advanced iPSC models that accurately mimic the complex tumor microenvironments and facilitate the study of tumor heterogeneity and therapeutic resistance.…”

“…This allows for the identification of novel compounds or combinations of drugs that are more effective in targeting cancer cells while minimizing the toxicity on healthy tissues [ 585 , 626 ]. iPSCs can also be genetically engineered to correct cancer-associated mutations or introduce therapeutic genes, providing a platform for gene therapy approaches [ 555 ]. Additionally, iPSCs can be utilized to produce immune cells with enhanced anti-tumor properties, facilitating the development of immunotherapies for cancer treatment.…”

“…Additionally, iPSCs can be utilized to produce immune cells with enhanced anti-tumor properties, facilitating the development of immunotherapies for cancer treatment. The versatility and adaptability of iPSCs make them a valuable tool in the development of innovative cancer therapies [ 555 , 606 ].…”