Pluripotent Stem Cell-Based Cell Therapy—Promise and Challenges

Yao

Rev Endocr Metab Disord

2021

Several therapeutic options have been developed to address the obesity epidemic and treat associated metabolic diseases. Despite the beneficial effects of surgery and drugs, effective therapeutic solutions have been held back by the poor long-term efficiency and detrimental side effects. The development of alternative approaches is thus urgently required. Fat transplantation is common practice in many surgical procedures, including aesthetic and reconstructive surgery, and is a budding future direction for treating obesity-related metabolic defects. This review focuses on adipose tissue transplantation and the recent development of cell-based therapies to boost the mass of energy-expenditure cells. Brown adipocyte transplantation is a promising novel therapy to manage obesity and associated metabolic disorders, but the need to have an abundant and relevant source of brown fat tissue or brown adipocytes for transplantation is a major hurdle to overcome. Current studies have focused on the rodent model to obtain a proof of concept of a tissue-transplantation strategy able to achieve effective long-term effects to reverse metabolic defects in obese patients. Future perspectives and opportunities to develop innovative human fat tissue models and 3D engineered hiPSC-adipocytes are discussed.

Section: Induced Pluripotent Stem Cell-based Therapymentioning

confidence: 99%

Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives

Yao

Rev Endocr Metab Disord

2021

“…Currently, somatic tissues undergo a reprogramming process using pluripotency-associated transcription factors, such as Oct3/4, Sox2, Nanog, and Lin28 [31]. The reprogrammed cells are known as human iPSCs (hiPSCs), and they can be re-introduced into patients without causing severe immune rejections [32,33]. hiPSCs attracted tremendous attention in therapeutic purposes, including cancer treatment and regenerative medicine, providing the opportunities to study the stem cell properties and the embryonic development process [34,35].…”

Section: Ipsc Overviewmentioning

confidence: 99%

Induced Pluripotent Stem Cells Provide an Unlimited T-cell Source for CAR-T cell Development and A Potential Source for Off-the-shelf Products

Nezhad

2021

Preprint

CAR-T cell therapy has been increasingly conducted for cancer patients in clinical settings. Progress in this therapeutic approach is hampered by the lack of a solid manufacturing process, T lymphocytes, and tumor-specific antigens. T-cell source used in CAR-T cell therapy is predominantly derived from the patient’s own T lymphocytes, which makes this approach impracticable to patients with progressive diseases and T leukemia. Autologous CAR-T cell generation is time-consuming due to lack of readily available T lymphocytes and is not applicable for third-party patients. Pluripotent stem cells, such as human induced pluripotent stem cells (hiPSCs), could provide an unlimited T-cell source for CAR-T cell development. iPSC-derived T cells would be a promising infinite T-cell source and are phenotypically defined, expandable and functional as physiological T cells. iPSC-derived T cells provide a feasible T-cell source for the development of off-the-shelf T cells and CAR-T cells. The combination of iPSC and CAR-Technologies provides an extraordinary opportunity to oncology and greatly facilitates cell-based therapy for cancer patients. T-iPSCs in combination with CAR is in early stage of development and the pre-clinical and clinical studies concerning the combination of these novel technologies are not sufficient. This article critically reviews the progress in iPSC-derived T cell development and provides a roadmap for development of CAR iPSC-derived T cells and off-the-shelf T-iPSCs. Keywords: CAR-T cell; iPSC; T cell; iPSC-derived T cell; tumor cell; therapeutic; off-the-shelf

“…To circumvent the barrier issues, autologous SC became an obvious choice for regenerative therapies. Yet, the demanding logistics to achieve immediate availability of sufficient numbers limited the potential use of autologous cells including iPSCs [3]. The well-documented ability of allogeneic adult SC to evade and/or regulate the host immune system comforted their consideration as a pragmatic choice that offers an efficient way for the development of off-the-shelf regenerative therapies with appropriate number of cells [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Stem Cells-Derived Extracellular Vesicles: Potential Therapeutics for Wound Healing in Chronic Inflammatory Skin Diseases

Manchon

Hirt

Bouaziz

et al. 2021

IJMS

Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their “cargo”, exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies. Yet, their clinical application is still facing considerable challenges, including production and isolation procedures, and optimal cell source. Within the emerging concept of “allogeneic-driven benefit” for SC-based therapies, the use of EVs from allogeneic sources becomes the pragmatic choice although a universal allogeneic cell source is still needed. As a unique temporary organ that ensures the mutual coexistence of two allogeneic organisms, mother and fetus, the human placenta offers a persuasive allogeneic stem cell source for development of therapeutic EVs. Advancing cell-free therapeutics nurtures great hope and provides new perspectives for the development of safe and effective treatment in regenerative/reparative medicine and beyond. We will outline the current state of the art in regard of EVs, summarize their therapeutic potential in the context of skin inflammatory disorders, and discuss their translational advantages and hurdles.