Recent Advances in Stem Cell and Cellular Therapies: From Hematological Malignancies to Regenerative Medicine (2020-2024)

Introduction

The past five years have witnessed significant advancements in stem cell and cellular therapies, expanding their application across various diseases. This mini-review highlights key progress in hematological malignancies, regenerative medicine, and the optimization of stem cell sources and delivery methods. We will focus on the evolution of CAR-T cell therapies for lymphoma and myeloma, the application of mesenchymal stem cells (MSCs) in regenerative medicine, and advancements in hematopoietic stem cell transplantation (HSCT) and gene therapy.

CAR-T Cell Therapy for Lymphoma and Myeloma: Efficacy and Optimization

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of relapsed or refractory large B-cell lymphoma (LBCL). Frederick L. Locke's research group has consistently demonstrated the efficacy of axicabtagene ciloleucel as a second-line therapy for LBCL, showing improved survival compared to standard of care (Jason R. Westin et al., 2022, New England Journal of Medicine; Frederick L. Locke et al., 2020, New England Journal of Medicine; Frederick L. Locke et al., 2021, New England Journal of Medicine). Manali Kamdar's group has explored lisocabtagene maraleucel as another effective second-line treatment option, including in patients not intended for HSCT (Alison R. Sehgal et al., 2022, The Lancet Oncology; Jeremy S. Abramson et al., 2022, Blood; Manali Kamdar et al., 2020, The Lancet; Manali Kamdar et al., 2021, The Lancet; Manali Kamdar et al., 2022, The Lancet). More recently, researchers are investigating strategies to improve CAR-T cell therapy outcomes, such as combining CAR-T cell therapy with high-dose therapy and autologous stem cell transplantation (Wei Liu et al., 2024, J. immunotherap. cancer). In multiple myeloma, Maximilian Merz's group has investigated the cellular dynamics following CAR-T cell therapy and their association with response and toxicity (Luise Fischer et al., 2024, Leukemia). Furthermore, He Huang's research highlights the potential of sequential CD7 CAR T-cell therapy and allogeneic HSCT without GVHD prophylaxis (Yongxian Hu et al., 2024, New England Journal of Medicine). However, Kai Rejeski's group has addressed the critical issue of immune effector cell–associated hematotoxicity, providing consensus grading and best practice recommendations (Kai Rejeski et al., 2023, Blood).

Mesenchymal Stem Cells (MSCs) in Regenerative Medicine: Mechanisms and Applications

MSCs have emerged as a promising therapeutic avenue in regenerative medicine due to their immunomodulatory and regenerative properties. Zucai Suo's group reviewed the applications of MSC-derived exosomes in regenerative medicine, highlighting their potential as cell-free therapeutic agents (Mangesh Dattu Hade et al., 2021, Cells). Hongjun Wang's group has further explored the clinical trials involving MSC-derived exosomes, noting their increasing use (Ahmed Lotfy et al., 2022, Stem cell res. ther.; Ahmed Lotfy et al., 2023, Stem cell res. ther.). Fei Tan's group has also reviewed the clinical applications of stem cell-derived exosomes, further emphasizing their therapeutic potential (Fei Tan et al., 2023, Signal Transduction and Targeted Therapy; Fei Tan et al., 2024, Signal Transduction and Targeted Therapy). The therapeutic potential of MSCs has been explored in various contexts, including COVID-19-induced ARDS (Seyed Mohammad Reza Hashemian et al., 2021, Stem cell res. ther.; Ismail Hadisoebroto Dilogo et al., 2021, Stem Cells Translational Medicine), neurological disorders (A Andrzejewska et al., 2020, Advanced Science; A Andrzejewska et al., 2021, Advanced Science), wound healing (Jiayi Yang et al., 2020, International Journal of Nanomedicine), rheumatoid arthritis (Chaoyang Li et al., 2024, Advanced Science), knee osteoarthritis (José Matas et al., 2024, Stem Cells Translational Medicine), and immune thrombocytopenia (Yunfei Chen et al., 2024, Signal Transduction and Targeted Therapy). Peter Timashev's group has investigated the cytokine and growth factor profiles of MSCs' conditioned media and their impact on macrophage polarization, providing insights into the mechanisms of action (Maria Peshkova et al., 2023, Stem cell res. ther.). Guido Moll's group emphasized the importance of assessing tissue factor and hemocompatibility of MSC products to maximize patient safety (Guido Moll et al., 2022, Stem Cells Translational Medicine).

Hematopoietic Stem Cell Transplantation (HSCT) and Gene Therapy: Expanding Applications and Improving Outcomes

HSCT remains a cornerstone of treatment for hematological malignancies and other disorders. Jakob Passweg's group, through the EBMT surveys, has provided valuable insights into the trends and activities in hematopoietic cell transplantation and cellular therapy over the past years (Jakob Passweg et al., 2020, Bone Marrow Transplantation; Jakob Passweg et al., 2021, Bone Marrow Transplantation; Jakob Passweg et al., 2024, Bone Marrow Transplantation). John A. Snowden's group has outlined the current practice in Europe regarding indications for HSCT (John A. Snowden et al., 2021, Bone Marrow Transplantation; John A. Snowden et al., 2022, Bone Marrow Transplantation). Gene therapy is also emerging as a curative option for several genetic diseases. Julie Kanter's group has demonstrated the biologic and clinical efficacy of lentiglobin for sickle cell disease (Julie Kanter et al., 2021, New England Journal of Medicine). Alessandra Magnani's group has shown the long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott–Aldrich syndrome (Alessandra Magnani et al., 2022, Nature Medicine). Haydar Frangoul's group has reported on the efficacy of exagamglogene autotemcel for severe sickle cell disease and transfusion-dependent β-thalassemia (Haydar Frangoul et al., 2023, New England Journal of Medicine; Haydar Frangoul et al., 2024, New England Journal of Medicine; Franco Locatelli et al., 2024, New England Journal of Medicine). André Lieber's group has demonstrated the potential of in vivo HSC prime editing to rescue sickle cell disease in a mouse model (Chang Li et al., 2023, Blood).

Conclusion

The field of stem cell and cellular therapies has rapidly evolved over the past five years. CAR-T cell therapy has become a standard of care for relapsed/refractory LBCL and is showing promise in myeloma. MSCs are being explored for their regenerative potential in various diseases, and HSCT and gene therapy continue to advance, offering curative options for genetic disorders. Future research should focus on optimizing these therapies, addressing safety concerns, and expanding their application to a wider range of diseases.

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