Preface

The need for effective translation in the field of stem cells is demonstrated by the small number of products on the market. This means a constant need to carry out basic research and to manipulate the properties of stem cells in such a way as to maximize their therapeutic effect while maintaining an appropriate level of safety of therapy. Thus, there is a serious disproportion between the demand and pressure from the patient and medical community and the ability of the market to provide safe and effective stem cell-based products. Mesenchymal stem cells (MSCs) are currently the most used type of stem cells in clinical trials. MSCs, also known as mesenchymal stromal cells [1] or medical signal cells [2], are adult stem cells with regenerative properties such as self-renewal, secretion of trophic factors, and ability to differentiate into other mesodermal lines. MSCs can also migrate and colonize the damaged site and secrete a number of trophic factors, modulating the immune system, influencing the microenvironment around damaged tissues, and improving endogenous tissue repair, thus offering a wide perspective in cell therapies. Therefore, MSCs are widely used in clinical trials. However, to date, several constraints have been identified in the development of clinical trials in stem cells [3]. The lack of knowledge, which led to the premature termination of several studies, can be considered obvious. However, there are many smaller but equally important obstacles. First, the quality of the obtained stem cells is important, which is influenced by many factors, such as selected isolation and culture methods. According to current data, MSCs are heterogeneous fractions that may contain a different fraction of "regenerative" cells. In addition, individual variability (e.g., sex, age, medical history, etc.) plays an important role here. Therefore, when choosing cells for a clinical trial, all parameters should be considered. In the clinicaltrials.gov database, there are three types of common sources of MSCs used in clinical trials, with almost 500 studies on bone marrow mesenchymal cells, more than 400 studies on adipose-derived mesenchymal cells, and almost 400 studies on umbilical cord mesenchymal cells. In addition, there are studies on mesenchymal cells isolated from the amniotic membrane [4]. Although the topic of mesenchymal cells isolated from hair follicles is extremely popular, there is not a single study on their clinical use in the database. MSCs can be isolated from virtually any tissue, however, for clinical use, a source is needed that provides a sufficient amount that is not defined by top-down standards, which makes MSC research very heterogeneous in terms of the number of cells applied. More than 800 studies on MSCs have been registered as phase I studies, although these calculations are subject to error in the form of registration of some studies in the phase I/II scheme. However, the number of studies does not translate to the number of products available to patients. This illustrates the constant need for research on stem cells and their shifting and reprogramming properties, which we cover in this book.

This book also examines issues of preparation and preservation of MSCs in translational research. Chapters describe organoids, nanotechnology, and exosomes. Exosomes isolated from MSCs have biological functions like those of MSCs, thus leading to tissue regeneration by encapsulating and transferring active biomolecules such as peptides, proteins, and RNA to diseased cells/tissues [5]. However, the use of MSC exosomes in clinical trials is limited due to the lack of established cell culture conditions and optimal protocols. Organoids from MSCs provide the appropriate functions and functionalities of the original native organs, which is essential for therapeutic application and drug screening [6]. Chapters also cover such topics as female germline stem cells, which are of particular importance in the face of growing fertility problems [7].

In the section on clinical applications, chapters discuss novel indications for stem cells and examine ethical concerns in stem cell research. They discuss induced pluripotent stem cells and targeting cancer stem cells. The clinical introduction of stem cells in pelvic floor disorders is presented as an example of practical application of stem cell therapy in an area that cannot be covered by other therapies.

This edited volume covers a wide diversity of problems, solutions, and translational issues that may accelerate future stem cell research.

> **Diana Kitala** Medical Research Agency, Warsaw, Poland

#### **References**

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[3] Musiał-Wysocka A, Kot M, Majka M. The Pros and Cons of Mesenchymal Stem Cell-Based Therapies. Cell Transplant. Jul 2019;**28**(7):801-812. DOI: 10.1177/0963689719837897

[4] https://clinicaltrials.gov/

[5] Nikfarjam S, Rezaie J, Zolbanin NM, et al. Mesenchymal stem cell derivedexosomes: A modern approach in translational medicine. Journal of Translational Medicine. 2020;**18**:449. DOI: 10.1186/s12967-020-02622-3

[6] Kim W, Gwon Y, Park S, Kim H, Kim J. Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration. Bioact Mater. 4 Apr 2022;**19**:50-74. DOI: 10.1016/j. bioactmat.2022.03.039

[7] Hong W, Wang B, Zhu Y, Wu J, Qiu L, Ling S, et al. Female germline stem cells: Aging and anti-aging. Journal of Ovarian Research. 4 Jul 2022;**15**(1):79. DOI: 10.1186/s13048-022-01011-2

Section 1
