Stem Cell Biology and Tissue Engineering Modalitie

Chapter 1: Classification of Stem Cells: Hierarchy, Origin, and Functional Diversity

Zahra Abbasi-Malati¹, Seyed Ghader Azizi^2*, Farzin Javid³, Reza Rahbarghazi³, Arian Maham³, Danial Mohammadnejad^3
1Medical Biotechnology Research Center, Paramedicine Faculty, Guilan University of Medical Sciences, Rasht, Iran
²Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
³Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to: Dr. Seyed Ghader Azizi (PhD); Email address: s.ghaderazizi@yahoo.com; Address: Clinical Immunology Research Center, Zahedan University of Medical Sciences, Zahedan, Iran

Abstract: Stem cells are heterogeneous and undifferentiated cells with the potential to differentiate into several lineages. From past decades to the present time, it has been shown that stem cells have an immense role in the conduction of in vitro studies and modeling of diseases. Different stem cell categories, such as TSCs , ESCs , and iPSCs, exhibit great potential for differentiation into the embryonic lineages of cells and therapeutic applications. Compared to these cells, multipotent stem cells, like HSCs , MSCs , and NSCs , possess a limited differentiation capacity but promote tissue repair and homeostasis in adults. Besides, prenatal stem cells like umbilical cord blood and WJ stem cells possess significant immunomodulatory properties. The emergence of sophisticated culture approaches such as organoid technology, CRISPR/Cas9 gene editing, and multi-omics analysis has improved the regenerative properties of stem cells and enabled interventions based on a person’s unique characteristics. Here, in this chapter, the taxonomy of stem cells with the application of various philosophical constructs in terms of the hierarchy of development potential, origin, tissue-specific functional diversity, and experimental characteristics will be discussed. Keywords: Stem cells; Potency Hierarchy, Pluripotency, Multipotency, Regenerative Medicine

Keywords:Stem cells; Potency Hierarchy, Pluripotency, Multipotency, Regenerative Medicine

Chapter 2: Cardiac progenitor cells in various cardiovascular diseases

Samaneh Narimani¹, Asma Gul², Masoud Khalifezadeh³, Reza Rahbarghazi^{1, 4*}, Sergey Suchkov⁵, Arian Maham^1
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
²Department of Biological Sciences, Faculty of Sciences, International Islamic University, Islamabad, Pakistan
³Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
⁴Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
⁵Zelinskii Institute for Organic Chemistry of the Russian Academy of Sciences, Moscow, Russia
Corresponding author: Reza Rahbarghazi (DVM, Ph.D.); E-mail: Rahbarghazir@tbzmed.ac.ir, Rezarahbardvm@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract:Cardiac ischemic diseases, especially myocardial infarction, are the main cause of human mortality and morbidity. Due to the irreversible tissue changes and lack of function in the affected area, rapid and timely medications and therapeutic protocols are mandatory to reduce post-myocardial infarction complications. Despite the magnificent progress in the health care system and therapeutics, the existence of unwanted side effects necessitates the development of novel medications. In this regard, enormous studies have been done to find highly efficient approaches with minimal complications in patients with myocardial infarction. Cardiac progenitor cells have been discovered in the heart within recent decades, with significant regenerative outcomes. Whether and how these cells can orchestrate the regeneration of ischemic myocardial tissue is at the center of the debate. 

Keywords:Cardiac progenitor cells; Cardiac ischemic changes; Cardiac regeneration; Angiogenesis; Regenerative Medicine.

Chapter 3: Hematopoietic stem cells in human medicine

Ali Rafat¹, Khadijah Dizaji Asl^2*, Zeinab Mazloumi^3
1Anatomical Sciences Research Center, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
²Department of Histopathology and Anatomy, TaMS.C., Islamic Azad University, Tabriz, Iran
³Department of Applied Cell Sciences, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to: Dr. Khadijah Dizaji Asl (PhD); Email address: kh.asli2013@gmail.com; Address: Department of Histopathology and Anatomy, TaMS.C., Islamic Azad University, Tabriz, Iran

Abstract:HSCs are multipotent cells responsible for the generation and reconstitution of all blood lineages. HSCs have played a central role in basic research and clinical treatments for hematological and genetic disorders. This review provides an overview of the historical evolution of hematopoietic research and highlights key milestones that led to the identification and functional characterization of HSCs. This review examines the molecular markers, developmental origin, and regulatory mechanisms that define HSC biology, as well as recent advances in their isolation, ex vivo expansion, and therapeutic use. Special attention is paid to clinical applications such as autologous and allogeneic transplantation, gene editing, and regenerative medicine, along with the ethical and immunological challenges associated with the use of HSCs. Finally, emerging strategies in personalized and regenerative therapies are discussed.

Keywords: Hematopoietic stem cells; Regeneration; Human.

Chapter 4: Natural Killer Cell-Based therapies

Zeinab Mazloumi^1*, Parisa Kangari^1
1Department of Applied Cell Sciences, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to: Dr. Zeinab Mazloumi (PhD); Email address: Zb.mazloumi@gmail.com; mazloomi@tbzmed.ac.ir; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract: NK cells are the main component of the innate immune system with the potential to function in immune surveillance and cytotoxicity against infected and malignant cells. Unlike B and T lymphocytes, NK cells can identify and eliminate abnormal cells without the necessity of prior sensitization. It is estimated that NK cells constitute about 5 to 15% of peripheral blood lymphocytes and are specifically immunophenotyped by surface markers such as CD56. In terms of activity, the balance between activating and inhibitory signals is critical in NK cytotoxic and immune-regulatory functions. In the last few years, the application of NK cells, as a promising tool for cancer therapy, has been extended in the clinical setting. Using various approaches, including NK cell engagers, monoclonal antibodies, and cytokine-based treatments, their cytotoxicity is enhanced. Novel approaches such as immune stimulants, CAR -engineered NK cells, and adoptive transfer of NK cells that have grown ex vivo are beneficial in the targeted recognition of tumor cells. Besides, NK cells and their products, such as EVs , exhibit putative anti-tumor impacts in preclinical research, opening new avenues for NK cell-based treatments. In this chapter, recent progress and implications regarding the application of NK cells have been discussed.

Keywords: NK cells; Cell-based therapies; Anti-tumor activities.

Chapter 5: Endothelial progenitor cells in cardiovascular diseases

Somayyeh Rashidi¹, Sara Aghakhani Chegeni², Golbarg Roozbahani³, Reza Rahbarghazi^4,5*, Fatima A. Karim^6
1Department of Medical Biotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
²Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
³Applied Cell Sciences Division, Department of Hematology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
⁴Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
⁵Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
⁶College of Dentistry, University of Al-Ameed, Kerbala, Iraq
Correspondence to Dr. Reza Rahbarghazi (DVM, Ph.D.); E-mails: rahbarghazir@tbzmed.ac.ir, rezarahbardvm@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract:The occurrence of ischemic diseases has increased in recent decades due to lifestyle changes. Along with the conventional therapeutic protocols, the development and emergence of novel modalities are at the center of debate to circumvent the pitfalls in the clinical setting. In recent years, the discovery of various stem cell types has helped biologists and clinicians alleviate diverse pathologies with relatively satisfactory outcomes. Among them, EPCs pave the way to accelerate the phenomenon of regeneration, especially in ischemic/hypoxic conditions. These cells exhibit prominent and bulk angiogenesis properties to re-establish the blood perfusion into the affected sites via direct differentiation into the mature ECs or release of angiogenesis factors. In this chapter, recent progress in the application of EPCs in CVDs was discussed in detail.

Keywords: Endothelial Progenitor Cells; Angiogenesis; Vasculogenesis; Ischemic Diseases

Chapter 6: Hematopoietic Source and Immune Cells in Cell-Based Therapy

Narjes Seddighi^1,2, Malihe Najafpour³, Atousa Ghorbani^4,5, Aysan Asefpour^6,7, Mahdi Talebi^*
1Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
²Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
³Department of Hematology, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran      
⁴Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
⁵Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran
⁶Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
⁷Department of Immunology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
⁸Department of Applied Cell Sciences, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to Dr. Talebi Mahdi (Ph.D.); E-mails: talebime@tbzmed.ac.ir, mt09143163667@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract:Immune cell-based therapies represent a rapidly advancing domain in biomedical research. Cellular sources, with emphasis on bone marrow-derived immune cells are included in this chapter. To this end, key cell types such as T, B cells, and NK cells are described in terms of immunological roles and therapeutic relevance. Particular attention is given to genetically engineered variants such as CAR-T and CAR-NK cells, which have demonstrated potent antitumor activity in hematological and solid malignancies. Besides, biotechnological strategies used for enhancing immune cell specificity, persistence, and cytotoxicity, including receptor engineering, cytokine modulation, and resistance to immunosuppressive signals, were discussed. Clinical trials highlighting the efficacy of CAR-T and CAR-NK therapies in targeting tumor-associated antigens were also included. The therapeutic efficiency and the dynamic interplay between infused immune cells and the host immune system were also highlighted. These insights underscore the need for integrated approaches using engineered cells and microenvironmental modulation to optimize outcomes in immune cell-based therapy.

Keywords: Natural Killer Cells; Immune Cell Therapy; Regenerative Medicine; Human

Chapter 7: Guardians of the Germline: The Origin and Regenerative Promise of Spermatogonial Stem Cells

Fatemeh Sokouti Nasimi¹, Shadi Atazadeh¹, Halimeh Mobarak², Ali Ibrahim Rahim Al-Dulaimi^3,4,5 Amin Tamadon⁶, Mahdi Mahdipour^{1, 7*
1}Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
²Department of Clinical Pathology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
³Department of Anatomy, Faculty of Medicine, University of Kufa, Najaf, Iraq
⁴College of Medicine, University of Al-Ameed, Karbala, Iraq
⁵Al-Kafeel IVF Center, Al-Kafeel Super-Specialty Hospital, Karbala, Iraq
⁶Department of Natural Sciences, West Kazakhstan Marat Ospanov Medical University, Aktobe, Kazakhstan
⁷Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
*Correspondence to Dr. Mahdi Mahdipour (Ph.D.), Address: Stem Cell Research Center, Tabriz University of Medical Sciences and Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Daneshghah St. Tabriz, 5166615739, Iran; Telefax: +98-41-3336-3870; E-mail:mahdipourm@tbzmed.ac.ir

Abstract:Spermatogonial stem cells form the basis of the male reproductive system and are unique cells with the ability to self-renew and differentiate, and are the only stem cells capable of transmitting genetic traits from one generation to the next. These cells differentiate into mature sperm after dividing through a special mechanism called spermatogenesis. Specific markers, including GPR125 and OCT-4, enable the isolation and identification of SSCs. The microenvironment of SSCs is located in the basement membrane of the seminiferous tubules and consists of various cell types and extracellular matrix that provide the factors and interactions necessary for the sustenance and function of the cells. Sertoli cells are one of the main components in the testicular microenvironment that are directly associated with SSCs and mediate protecting, nourishing, proliferation, and differentiation of germ cells via secreting various types of factors. Isolation, culture, and cryopreservation of SSCs are used as a method to treat some cases of infertility. Today, stem cell-based therapies such as SSCs transplantation to restore fertility in cancer patients and in vitro spermatogenesis are one of the most promising tools in improving male fertility.

Keywords: Spermatogonial stem cells, Spermatogenesis, Self-renewal, Differentiation, Therapeutic applications

Chapter 8: Neural stem cells application for central nervous system pathologies

Behnaz Mirzaahmadi^{1, 2}, Parinaz Haddadi¹, Reza Rahbarghazi^{1, 2}, Mohammad Karimipour^{1, 3*
1}Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
²Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
³Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
^*Corresponding to Dr. Mohammad Karimipour (Ph.D.); E-mail: karimipourm@tbzmed.ac.ir, karimipourm@yahoo.com; Address: Department of Anatomical Sciences, Tabriz University of Medical Sciences, Daneshghah St. Tabriz, 5166614766, Iran; Telefax: +984133342086;

Abstract: The discovery and advent of NSCs in preclinical and clinical studies have led to progress in the alleviation of several pathological conditions. NSCs are rare cell numbers of the CNS and are located in the SVZ and the hippocampal DG in adults and mature rodents. To date, the number of studies related to the application of NSCs in animals and human counterparts has increased. It has been suggested that NSCs can efficiently directly commit to neuronal cells to restore function or replace injured neurons or glia. Besides, the release of several cytokines and growth factors facilitates the neuroregeneration following transplantation into the injured sites. Here, in this chapter, the therapeutic properties of NSCs will be discussed under pathological conditions related to neurodegeneration or ischemic diseases. Understanding the molecular mechanisms provided by transplanted NSCs can help us in the development of nascent therapeutic protocols.

Keywords: Neural Stem Cells; Neurodegeneration; Ischemic Changes; Therapy; Regenerative Medicine.

Chapter 9: Extracellular vesicles as an alternative modality to stem cell-based therapies

Leila Salimi^{1, 2}, Banafsheh Yalameha¹, Mahdi Akbari Soufiani³, Rasoul Hosseinpour⁴, Narges Mardi¹, Reza Rahbarghazi^{1, 2*
1}Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
²Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
³Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
⁴Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to Dr. Reza Rahbarghazi (DVM, Ph.D.); E-mails: rahbarghazir@tbzmed.ac.ir, rezarahbardvm@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract:The increase in stem cell transplantation in different pathologies has led to progress in the control and healing of patients in the clinical setting. The isolation and expansion of stem cells need various in vitro technologies before grafting into the injured tissues. Therefore, finding suitable substitutes with a therapeutic potential similar to the whole stem cells is highly recommended. In most circumstances, allogeneic stem cell sources are used for regenerative purposes, which can increase the possibility of rejection by allo-reactive immune cells. The discovery of EVs with relatively similar regenerative potential to the parent stem cells has led to enhanced regenerative outcomes and a reduction of immune system rejection. Here, in this chapter, we discussed details about the biology and characteristics of EVs in biomedicine and regenerative medicine.

Keywords: Extracellular Vesicles; Exosomes; Biogenesis; Theranostics.

Chapter 10: Embryonic stem cells in cardiac tissue regeneration; concept and application

Leila Salimi¹, Hadi Sadeghzadeh²*, Roya Shabkhizan³, Reza Rahbarghazi^3,4*
¹Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
²Department of Tissue Engineering, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
³Department of Applied Cell Science, Faculty of Advanced Medical Science, Tabriz, Iran
⁴Stem Cell and Regenerative Medicine (SCARM), Tabriz University of Medical Sciences, Tabriz, Iran
^*Corresponding author: Hadi Sadeghzadeh (Ph.D.); Email:sadeghzadeh.nigeb@gmail.com; Address: Department of Tissue Engineering, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.
Corresponding author: Reza Rahbarghazi (DVM, Ph.D.); E-mail: Rahbarghazir@tbzmed.ac.ir, Rezarahbardvm@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract:Due to their unique pluripotent properties, ESCs are a crucial component of regenerative therapy. ESCs, which are derived from the inner cell mass of blastocysts, can develop into any cell, providing unheard-of possibilities for organ regeneration and tissue repair. With a focus on myocardial regeneration, this review examines the theoretical underpinnings and therapeutic uses of ESCs. Cardiovascular disorders, especially myocardial infarction, are a leading cause of morbidity and mortality globally and result in the irreparable loss of cardiomyocytes. A promising approach to cardiac tissue engineering is provided by ESC-derived cardiomyocytes, which allow injured myocardium to be replaced and heart function to be restored. Significant obstacles still exist, nevertheless, such as immunogenicity, teratoma development risk, and host tissue integration. These restrictions are being addressed by ongoing research using techniques including genome editing, scaffold-based delivery systems, and guided differentiation. Finally, ESC-based cardiac therapies have the potential to completely transform the way heart disease is treated and represent a new frontier in customized regenerative medicine.

Keywords: Embryonic Stem Cells; Regenerative medicine; Myocardial disease

Chapter 11: Embryonic Stem Cells in Human Medicine; terminology and application

Sima Esmaeili¹, Mina Ebrahimi², Zeinab Aliyari Serej^2*
1Department of Exercise Physiology, Faculty of Educational Sciences and Psychology, Azerbaijan Shahid Madani University, Tabriz, Iran
²Department of Applied Cell Sciences, Faculty of Advanced Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to Dr. Zeinab Aliyari Serej (Ph.D.); E-mail: z.aliyari64@gmail.com; z_aliyari@yahoo.com Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.

Abstract: hESCs possess remarkable self-renewal and pluripotency, enabling differentiation into cell types from all three germ layers. Since their isolation in 1998, hESCs have offered significant potential for tissue repair and regenerative medicine, disease modeling, drug testing, and genetic engineering. However, challenges persist, including tumorigenicity, immune rejection, ethical concerns surrounding embryo destruction, and regulatory hurdles. The document reviews derivation methods, culture systems (including feeder-dependent and feeder-free, xeno-free and GMP-compatible conditions), and strategies to maintain genomic stability, as well as clinical applications across tissue engineering, disease modeling, and personalized medicine. It also discusses developmental biology context, directed differentiation protocols, quality control, and the regulatory/ethical landscape, highlighting ongoing advances such as naive pluripotency, organoid models, CRISPR-based genome editing, and scalable bioprocessing for translational therapies.

Keywords: Embryonic stem cells, Inner cell mass, Tumorigenicity and safety, Regenerative medicine, Disease modeling, Drug testing and toxicology.

Chapter 12: Cancer stem cells: terminology and implications in clinical cancer biology

Fereshteh Vaziri Nezamdoust¹, Parisa Mohammad-Jafarieh², Reza Rahbarghazi^{2, 3*
1}Stem Cell and Regenerative Medicine Institute (SCARM), Tabriz University of Medical Sciences, Tabriz, Iran
²Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
³Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
^*Correspondence to: Dr. Reza Rahbarghazi (PhD); Email address: rezarahbardvm@gmail.com; rahbarghazir@tbzmed.ac.ir; Telefax: +98-41-3335678; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Golghasht St., Tabriz, Iran. Postal code: 5657700-34344.

Abstract:The advent and discovery of CSCs have revolutionized our understanding of tumor cell biology, activity, and efficiency of various therapeutic protocols. CSCs with specific properties such as stemness features, self-renewality, and differentiation capacity can control the development, progression, and metastatic behavior even in the presence of conventional therapeutic regimes. Several studies have revealed that CSCs can produce different cell lineages within the tumor parenchyma, leading to therapy resistance and relapse. These cells can engage various intracellular signaling pathways to adapt themselves to the insulting conditions and circumvent the therapeutic protocols to preserve their entities, resulting in the production of enormous neoplastic cells. Here, in this chapter, recent data about CSC features and behavior in the context of tumors will be discussed. Data in this chapter can help us in the proper understanding of CSC biology, activity, and their relevance to tumor development and progression, which is highly significant in human medicine and the selection of correct therapeutic protocols.

Keywords: Tumors; Cancer stem cells; Dynamic Growth and Activity; Therapy.

Chapter 13: Laser technology in medicine: types, mechanisms, and applications with a focus on stem cell biology and regenerative medicine

Hesam Saghaei Bagheri^1,2, Reza Rahbarghazi^1,2*, Çığır Biray Avci^3*
1Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
²Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 
³Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey
^*These authors contributed equally to this work.
*Correspondence to Dr. Reza Rahbarghazi (DVM, Ph.D.); E-mails:rahbarghazir@tbzmed.ac.ir rezarahbardvm@gmail.com; Address: Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, 5166653431, Tabriz, Iran.
*Correspondence to Dr. Çığır Biray Avci (Ph.D.); E-mails:cbavci@gmail.com cigir.biray@ege.edu.tr; Address: Department of Medical Biology, Faculty of Medicine, Ege University, Izmir, Turkey.

Abstract: Laser technology has profoundly restructured the biomedical field by providing selective, minimally invasive therapeutic interventions. Lasers with quantum electronics principles can generate coherent, monochromatic light with the potential to influence microorganisms. Recent data have confirmed the putative stimulatory and inhibitory role of laser irradiation on the regulation of different stem cell bioactivities and obtaining regenerative outcomes. The potential effect of laser irradiation on stem cell differentiation capacity, paracrine activity, proliferation, dynamic growth, etc., has been proven using several in vitro, pre-clinical, and clinical studies. Therefore, laser technology can be used as a complementary and alternative approach in the control of cell therapy efficiency. Here, in this chapter, we aimed to illuminate laser applications through stem cell and regenerative biology. Remarkably, the advent of LLLT as a non-thermal light-based technique with positive effects on different cell activities will be discussed. Data from the current chapter can help us in the translation of laser technology to the clinical setting with cutting-edge advances to improve stem cell-based therapy outcomes.
Keywords: Low-level Laser Irradiation, Stem Cells, Cell Therapy, Regenerative Medicine.

Chapter 14: An Update to Approved Cell, Gene, and Tissue Therapy Products

Shukoofeh Torabi^1,2*,Akbardoust‏^1,2
1Anatomical Sciences Research Center, Institute Basic Sciences, Kashan Sciences, Kashan, Iran
² Applied Sciences, Faculty of Medicine, Kashan of Medical Sciences, Kashan, Iran
to Dr. Shukoofeh (Ph.D.). Email: Torabi-sh@kaums.ac.ir; Address: Sciences Research Center, Sciences, Kashan University of Medical Sciences, Kashan, Iran.

Abstract:CGTPs are distinct therapeutic products intended for human use to provide cures, prevention, palliative care, or diagnostic functions. Currently, these therapeutic approaches are revolutionizing medical science by targeting previously incurable diseases, including inherited genetic disorders, blood-related diseases, malignancies, and neurodegenerative disorders. Additionally, clinical practices have progressively shifted towards these products. The latest analysis by the Alliance for Regenerative Medicine reports 2,125 clinical trials for CGTPs up to November 2025. In this part of the book, based on available information from regulatory agencies and relevant companies’ websites, articles, and other data sources, we provide an in-depth discussion of classified CGTPs, including the product’s description, manufacturer, indications, approval dates, and the corresponding regulatory agency.

Keywords: Stem Cells; Cell Therapy; Products; Clinical Trials.

Chapter 15: Clinical Perspectives on Mesenchymal Stem Cell-Based Regenerative Medicine: Source Diversity, Plasticity, Immunomodulation, and Therapeutic Mechanisms

Parisa Kangari^1*, Mazloumi¹, Fereshteh Vaziri Nezamdoust^1 
1Department of Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University Medical Sciences, Tabriz, Iran
*Correspondence to Dr. Parisa Kangari (PhD). Email address: pk_biology@yahoo.com; Address: Department of Applied Sciences, Faculty of Medical Sciences, Tabriz University of Sciences, 5166653431, Tabriz, Iran. 

Abstract: MSCs are multipotent stem cells derived from embryonic mesoderm and neural crest, capable of self-renewal and giving rise to several mesenchymal lineages, including osteoblasts, adipocytes, chondrocytes, myocytes, etc. Human MSCs were first identified in adult bone marrow as fibroblast-like cells and then were isolated from diverse sources, including adipose tissue, skin, UC , WJ , dental tissue, various biofluids such as amniotic fluid, synovial fluid, cerebrospinal fluid, breast milk, and urine. Each source provides unique benefits in terms of accessibility, proliferation, and regeneration potential. Even though UC MSCs exhibit higher stemness properties with prominent differentiation capacity. Although donor factors, tissue origin, and culture conditions all can affect the biological heterogeneity of MSCs, the isolated cells share characteristics such as plastic adherence, CD105, CD73, and CD90 expression, lack of hematopoietic markers, and trilineage differentiation in accordance with ISCT criteria. Preclinical and clinical studies, including trials for multiple sclerosis, osteoarthritis, heart disease, and COVID-19 , have demonstrated their efficacy in immune modulation and regeneration, though challenges like heterogeneity and optimal sourcing persist. Along with these descriptions, it is thought that MSCs hold immense promise for regenerative medicine, with exosomes emerging as safer alternatives.

Keywords: Mesenchymal stem cells; Regenerative medicine, Immunomodulation, Exosomes, Plasticity