Preface

**Section 2 Stem Cells in Disease 109**

**VI** Contents

and Biljana Mihaljevic

Aisha Nasef

Chapter 7 **Stem Cell-Based (Auto)Grafting: From Innovative Research Toward Clinical Use in Regenerative Medicine 111**

Chapter 8 **Hematopoietic Stem Cells in Chronic Myeloid Leukemia 137**

Chapter 9 **Role of Bone Marrow Derived Mesenchymal Stem Cells in Management of Graft Versus Host Disease 165**

Moreno-Lorenzana and Héctor Mayani

Antonieta Chávez-González, Sócrates Avilés-Vázquez, Dafne

Bela Balint, Slobodan Obradovic, Milena Todorovic, Mirjana Pavlovic

Stem cells have a prominent role in biology of normal life and also in pathogenesis of diseases.

Life starts with generation of an embryo (the most primitive form of a stem cell) and goes through all of the embryonic and fetal stages of life. It forms all of the tissue and organs of a living organism and then has a role in maintenance of normal cellular composition of body. And finally these cells maintain body in a steady state of cell loss and substitution of normal lost/died cells by new normal cells.

Nearly in every organ of body we have these cells, although location characteristic and bio‐ logical property of them is not completely understood.

Despite of their role in normal life, these cells also have a prominent role in many diseases. Deficiency/depletion of these cells is very important in pathogenesis diseases. For example aplastic anemia (a fatal form of hematopoietic stem cell disease) is stem cell damage in bone marrow, due to environmental or immunologic dysregulation.

Cancer is also a stem cell disease. Genetic/metabolic abnormalities of tissue stem cells (or some times more mature progenitor cells) may disrupt normal proliferation of immature cells in an organ and start process of carcinogenesis.

Although clinical application of the best known stem cells (Hematopoietic stem cells) is pos‐ sible today and they are useful for treatment of many malignant and non-malignant disor‐ ders, clinical knowledge and application of these cells is in infancy. These cells are potentially applicable in regenerative medicine and also cancer treatment.

For safe and effective application of these cells, we need better knowledge of their biology, their interaction with other cells (especially supporting niche cells), growth, maturation and also immigration of stem cells through body in normal and abnormal conditions. Also for clinical application we need to know their characterization, their separation methods and safe manipulation.

This book is written to clarify some aspects of stem cell biology, their characteristics, assess‐ ment of damage to cells during ex vivo manipulation and also their role in a model of can‐ cers (chronic myeloid leukemia).

#### **Kamran Alimoghaddam, MD.**

Institute for Oncology, Hematology and Stem Cell Transplantation Tehran University of Medical Sciences, Tehran, Iran

**Section 1**

**Stem Cell Biology**

**Section 1**

**Stem Cell Biology**

**Chapter 1**

**Regulators of the Proliferation of**

Additional information is available at the end of the chapter

Yasushi Kubota and Shinya Kimura

http://dx.doi.org/10.5772/55639

**1. Introduction**

(e.g., CD34low/- Kit+

**During Hematopoietic Regeneration**

**Hematopoietic Stem and Progenitor Cells**

Adult hematopoietic stem cells (HSCs) ensure the maintenance of the HSC pool via their selfrenewal capacity, and replenish mature cells throughout life via their proliferation and differentiation into lineage-restricted cells [1, 2]. HSCs are the only stem cells that have been used in the clinic to treat diseases, such as leukemia, germ cell tumors, and congenital immunodeficiencies. Since HSCs were first proposed [3], advances in multicolor flow cytom‐ etry have allowed the purification of mouse HSCs close to homogeneity. Several groups have succeeded in long-term hematopoietic reconstitution by transplanting a single lineage of HSCs

Sca-1+ lineage marker-negative cells and CD150+

that divide only about five times throughout the mouse life span [8, 9].

marker-negative cells), providing direct proof of the existence of HSCs [4-7]. More recently, two groups analyzed the cycling status of HSCs by monitoring their proliferation rate over several months in vivo. The results of these studies suggested the presence of dormant HSCs

In the bone marrow (BM), HSCs are located in a specialized microenvironment, called the niche. Under steady-state conditions, signals from niches maintain some HSCs in a dormant state. Acquisition of dormancy is critical for the preservation of the self-renewal ability of HSCs and for the prevention of premature stem cell exhaustion [10-12]. However, in response to external stresses, such as bleeding, myeloablative chemotherapy and total body irradiation, HSCs proliferate extensively to produce very large numbers of primitive progenitor cells, thereby enabling rapid hematological regeneration [13]. Once recovery from myelosuppres‐ sion or other stresses has been achieved, the activated HSCs return to a quiescent state via a number of negative feedback mechanisms [14]. This ability is a hallmark of HSCs and is

and reproduction in any medium, provided the original work is properly cited.

© 2013 Kubota and Kimura; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

CD48-

Kit+

Sca-1+

lineage

**Chapter 1**
