Stem Cells in Clinical Application and Productization

Stem cells of hierarchical clustering have emerged as alternative and promising sources for tissue engineering and regenerative medicine. Owing to the unique self-renewal and multi-lineage differentiation attributes, stem cell-based cytotherapy has evoked great expectations in handling numerous refractory and recurrent diseases. Of note, quality control (QC), good manufacturing practice (GMP), and guidelines for stem cells and the derivations are prerequisites for evaluating the safety and efficacy of stem cell-based remedies. In this book, we principally focus on the definition, classification, signatures and functions, safety and efficacy of stem cells, together with the core concerns upon stem cell-based clinical applications and investigational new drug (IND) and new drug application (NDA). Collectively, this book will effectively benefit the novel stem cell-based tissue engineering and regenerative medicine.

Longitudinal studies have indicated the involvement and performance of multitudinous biomaterials for stem cell-based cytotherapy and regenerative medicine largely attribute to their specific biocompatibility. Currently, stem cells and biomaterial scaffolds have been considered as the two essential elements of the cornerstone of tissue engineering. On the one hand, biomaterials are beneficial to provide suitable microenvironments for enhancing the cellular vitality and therapeutic effect of stem cells. On the other hand, biomaterial-induced fibrosis and inflammation remain a prominent challenge in designing and synthesizing appropriate materials to facilitate tissue repair and organ regeneration. In this book chapter, we summarize the classification and physicochemical properties of the indicated biomaterials, and appraise the latest literatures of biomaterial and stem cell composite for broad biomedical applications in tissue engineering and regenerative medicine. Collectively, we retrospect the current advancement of biomaterial engineering and science, and highlight the multifaceted biomaterial-assisted stem cell-based tissue engineering and regenerative medicine, and in particular, the biomaterial-based composites with mesenchymal stem/stromal cells (MSCs) and the derivatives (e.g., exosomes, small microvesicles) for intractable disease administration.

Hematopoietic stem cells (HSCs) are a common origin of blood cells and the intermediate progenitor cells and precursor cells including the myeloid or lymphoid lineages, which are the footstones of short-term and long-term blood regeneration. HSCs are precisely orchestrated by the constituents in the hematopoietic microenvironment in the bone marrow niches such as stromal cells, immune cells, and cytokines. The dysfunction and genetic variations of HSCs might lead to hematopoietic abnormality, haematopoietic equilibrium and even hematologic malignancies. Meanwhile, the cellular and molecular mechanisms of HSC maintenance and differentiation according to the niche are of great importance for disease administration via hematopoietic stem cell transplantation (HSCT). In the chapter, we mainly focus on the works of literature on the definition, biological phenotypes, preclinical investigation and clinical trials of HSCs, which will collectively facilitate the clinical application of HSCT and the relative regenerative medicine for hematological diseases and immune diseases in future.

Neural stem cells (NSCs) are unique subsets of stem cells with self-renewal and multiple lineage differentiation potential, which are considered promising cell sources for neuron generation and complex cognitive and sensory functions, and the resultant NSC-based cryotherapy for regenerative purposes. Of them, distinguished from the small amount of activated subset, most of the NSCs are maintained in the quiescent state and reveal a low level of metabolic activity but a high sensitivity to the environment. The dynamic balance between quiescence and the activity of NSCs determines both the efficiency of neurogenesis and the long-term maintenance and self-renewal of the NSC pool as well as the neurogenic capacity of the brain. In this chapter, we mainly review the classification and biofunction of NSCs, and introduce the significant progress in the understanding of NSC-based applications and the underlying molecular mechanism for NSC quiescence, the dysfunction in neurogenesis, and the pathogenesis of neurological disorders. Collectively, these data will facilitate the development of NSC-based cytotherapy for a broad spectrum of refractory and recurrent diseases in the future.

Mesenchymal stem/stromal cells are splendid cell sources for tissue engineering and regenerative medicine attributed to the unique hematopoietic-support and immunomodulatory properties as well as the multi-dimensional differentiation potential towards adipocytes, osteoblasts, and chondrocytes in vitro and in vivo. To date, MSCs have been identified from various approaches, such as perinatal tissues, and adult tissues, and even derived from human pluripotent stem cells (hPSCs). Longitudinal studies have indicated the ameliorative effect and therapeutic efficacy upon a variety of refractory and recurrent disorders such as acute-on-chronic liver failure (ACLF), acute myeloid leukemia (ACLF), premature ovarian failure (POF), and intractable wounds. To date, MSCs have been a to have various origins, including mesoderm, endoderm and ectoderm. In this chapter, we mainly focus on the concepts, and biological and therapeutic properties of MSCs, together with the standardizations for industrial transformation. Overall, the descriptions would help promote a better understanding of MSCs in disease pathogenesis and management and benefit the preclinical and clinical applications in the future.

Stem cells are a category of cells with self-renewal and multi-lineage differentiation capacity, which have been recognized as advantaged sources for tissue engineering and regenerative medicine. To date, stem cells and their derivatives alone or combined with biomaterials have aroused extensive and sustained attention to investigations in the field of fundamental research and clinical practice. In recent years, a series of novel technologies have been involved in stem cell-based cytotherapy, such as three-dimensional (3D) printing, organoid research, and multitudinous kinds of gene-editing technologies, which collectively facilitate the development of tissue engineering for disease administration. In this chapter, we summarized the rudimentary knowledge of the aforementioned new technologies, together with the promising perspective and the concomitant challenges, which would help increase the cognition of technological innovation for stem cell-based investigations and remedies in the future.

Mesenchymal stem/stromal cells (MSCs) can be used as a therapeutic agent in regenerative medicine, owing to their unique self-renewal, multi-lineage differentiation, and immunoregulation properties. The manufacturing of authorized MSC products should depend on good manufacturing practices (GMP), Good Laboratory Practice (GLP), and Good Clinical Practice (GCP). Until now, many biotech companies have invested in developing the clinical application of MSC product all over the world. Meanwhile, the application of MSC products for human use must comply with regulations and guidance for a biotech company. In this chapter, we discuss the process and development of MSC products from production-manufacturing to commercialization.