Preface

Regenerative medicine is a promising interdisciplinary field that applies basic principles of engineering and life sciences to repair, replace, or regenerate damaged or lost tissues and organs. Unlike conventional medicine, regenerative medicine uses human cells and other substances to regrow tissues or restore their functions. An important characteristic of regenerative medicine is that its effects, if not permanent, are long lasting. The main aim of regenerative medicine is to use culturing methods to develop techniques and products using the body's own cells for medical treatment. Regenerative medicine combines approaches such as the use of cell-based, cell-free soluble molecules, stem cells from different sources, gene therapy, tissue engineering, reprogramming of cells and, more recently, cell-free regenerative therapies. This book, *Regenerative Medicine*, provides details of recent advancements in regenerative therapies for regenerative medicine applications.

Regenerative medicine therapies have gained significant popularity in recent years and have provided novel therapeutic approaches for a number of diseases. This book examines research in bone marrow aspirates, adipose tissue-derived stem cells and growth differentiation factor 11, platelet-rich plasma, and nanowires for use in regenerative medicine applications. Chapters focus on the use of stem cells (specifically mesenchymal stem cells derived from bone marrow or adipose tissue) and platelet-rich plasma for regenerative purposes. In addition, the book discusses regenerative medicine applications for eyes, skin, musculoskeletal disorders, spinal disorders, critical limb ischemia, and joint degeneration. Further, it covers the role of hypoxic preconditioning as a strategy to enhance the regenerative potential of stem cells. The chapter by Dr. Everts et al., "The Rationale and Roles of Autologous Prepared Bone Marrow Aspirate Concentrate Cells in Regenerative Medicine Applications," highlights the applications of autologous bone marrow-derived concentrate in regenerative medicine. This chapter begins with a brief introduction of stem cells and their different types and addresses the cellular contents of bone marrow tissue, harvesting, and preparation techniques. In addition, this chapter further discusses characteristics of bone marrow-derived mesenchymal stem cells and their applications in musculoskeletal disorders, spinal disorders, chronic wounds, and critical limb ischemia.

The chapter "Adipose-Derived Stem Cells (ADSCs) and Growth Differentiation Factor 11 (GDF11): Regenerative and Antiaging Capacity for the Skin" by Dr. Mazini et al. describes how ADSCs cross-react with GDF11 to assure dermal fibroblasts' and keratinocytes' proliferation to reverse the aging process. It also discusses the involvement of cell signaling pathways related to GDF11 and TGF-β in balancing cell rejuvenation and cell regeneration as well as skin anatomy, mechanism of skin aging, role of ADSCs in skin rejuvenation, and interactions of ASDCs with TFG-β and GDF11 for skin regeneration. Finally, the chapter presents immunomodulatory effects and antiaging mechanisms of ADSCs with respect to TFG- β and GDF11.

"Isolation, Activation and Mechanism of Action of Platelet-Rich Plasma and its Applications for Joint Repair" by Dr. Sanchez et al. highlights the importance

of platelet-rich plasma (PRP) use for joint repair. This chapter describes joint physiology and the process of joint degeneration followed by a description of PRP as a bioactive source. It also discusses in detail methods of PRP isolation and preparation, its types, and process of activation. Finally, the chapter describes the therapeutic potential of PRP in joint degeneration and its clinical translation.

In "Regenerative Medicine and Eye Diseases," Dr. Vingolo et al. examine the use of stem cells in ophthalmological pathologies affecting both the anterior and posterior eye segments. The authors review the most relevant clinical trials describing the role and potential of stem cell-based regenerative therapy in corneal and retinal pathology. They also analyze and comment on the results of scientific literature and possible side effects related to the use of stem cell therapy. Further, the chapter describes the route of cell administration and role of regenerative medicine in the anterior and posterior segments of the eye. Finally, the authors share their experience of cell therapy in atrophic retinal diseases.

"Applications of Nanowires for Retinal Diseases" by Dr. Kharaghani et al. provides an introduction of retinal anatomy, retinal disorders, and the latest progress in the research for retinal regeneration and vision using nanowires. In addition, the chapter examines different structures including core-shell and functionalized nanowires with nanoparticles. It also describes the nanowire-based mechanism of retinal regeneration along with challenges and prospects of its use.

In the final chapter, "Hypoxic Preconditioning as a Strategy to Maintain the Regenerative Potential of Mesenchymal Stem Cells," Dr. Bashir et al. discuss hypoxic preconditioning for improving regenerative potential of stem cells. In this chapter, the authors describe how regenerative potential of stem cells is compromised by age of donor and in vitro passaging, and how hypoxic preconditioning could be employed to enhance the age- and passage-depleted function of stem cells.

Although my name appears on this book's cover, I am grateful to the wonderful work of all the authors who contributed chapters. I am also grateful for the support provided by the staff at IntechOpen. I would like to thank my brother Muhammad Hanif for his continuous support and my wife Ruhma Mahmood Choudhery for her assistance and support. Thanks to all my students at King Edward Medical University and those who worked with me at University of Arizona, USA. Thanks also to Professor David T. Harris for his sincere advice and belief in me.

> **Dr. Mahmood S. Choudhery, PhD** King Edward Medical University, Lahore, Pakistan

> > **1**

**1. Introduction**

**Chapter 1**

**Abstract**

Applications

*and Kenneth Mautner*

the effects of BMA concentration.

**Keywords:** regenerative medicine, bone marrow aspiration, niche

cells, mesenchymal stem cells, differentiation, immunomodulation

microenvironment, bone marrow concentrate, centrifugation, hematopoietic stem

The objectives of regenerative medicine applications are to support the body to form new functional tissues to replace degenerative or defective ones and to provide therapeutic treatment for conditions where conventional therapies are inadequate. The human body has an endogenous system of regeneration through stem cells,

The Rationale of Autologously

Aspirate Concentrate for use

*Peter A. Everts, Glenn Flanagan II, Joshua Rothenberg* 

Autologously prepared bone marrow aspirate concentrates, have the potential to play an adjunctive role in various patient pathologies that have not been able to heal with conventional treatment modalities. The use of bone marrow aspirate (BMA) and concentrates in regenerative medicine treatment plans and clinical applications is based on the fact that bone marrow cells, including progenitor and nucleated cells, platelets, and other cytokines, support in tissue healing and tissue regenerative processes. The use of concentrated BMA cells focuses primarily on mesenchymal stem cells (MSCs), with the ability to self-renew and differentiate into multiple cell types. Concentrated bone marrow cells can be retrieved from harvested BMA and ensuing minimal manipulative cell processing techniques, executed at point of care (POC). The application of bone marrow biological therapies may offer solutions in musculoskeletal pathologies, spinal disorders, chronic wound care, and critical limb ischemia (CLI), to effectively change the local microenvironment to support in tissue healing and facilitate tissue regeneration. This chapter will address the cellular content of bone marrow tissue, harvesting and preparation techniques, and discuss the biological characteristics of individual marrow cells, their inter-connectivity, and deliberate on

Prepared Bone Marrow

in Regenerative Medicine
