3.2. Importance and uses

MSCs produce many growth factors and essential cytokines needed for cell proliferation and differentiation [19]. They also support hematopoiesis in bone marrow and play an indirect role in supporting other cell types during tissue repair [20]. Adult stem cells could overcome many of the ethical and technical debate associated with ESC as they are isolated from adult tissues, including bone marrow stromal cells, adipose-derived stem cells and adult skin stromal cells [21]. However, because of their limited differentiation potential (multipotent), they are less likely to form tumors, although some are thought to be related to certain tumors [22].

### 3.3. Location

lineage are described as unipotent [2]. In the trilaminar embryo, a middle mesodermal layer is formed between the ectodermal and endodermal cell layer. This mesodermal cell layer contains mesenchymal stem cells (MSCs), which develop into connective tissue (mesenchyme) and

Embryonic stem cells (ESCs) have the greatest potential to differentiate into all cell types. ESCs are derived from the inner cell mass of the blastocysts. However, the use of ESC is associated with several ethical issues [4]. Also, safety concerns were raised with a high incidence of

Induced pluripotent stem cells (iPS) were first achieved by inducing a forced expression of specific genes that can reprogram human and mouse adult somatic cells into the undifferentiated cell [6, 7]. iPS have the same characteristics of ESCs, such as expression of pluripotency markers

Fetal stem cells (FSCs) are derived either from a fetus or from extraembryonic structures. Various subtypes of FSCs were described according to their origin (i.e., amniotic fluid, umbilical cord, Wharton's jelly, amniotic membrane, and placenta). FSCs are ideal sources of cells for use in regenerative medicine. They are easily accessible, having a high proliferation rate. In addition, FSCs do not form teratomas [8] and overcome the ethical problem associated with ESCs [9].

In principle, adult stem cells are unspecialized (undifferentiated) cells. They are found in differentiated tissues and considered to be quiescent, but still capable of self-renewal and differentiation. These cells remain in their undifferentiated state until stimulated [10]. Adult MSCs have been isolated from different sites: bone marrow, adult peripheral blood, tooth pulp and liver [11].

The concept of mesenchymal stem/stromal cells (MSCs) was first introduced about half a century ago. In the 1970s, [12] Alexander Friedenstein described a population of bone marrow-derived cells of mesodermal origin. These MSCs were shown to have the ability to self-renew and to

it maintains the progenitor stem cells that persist after birth [3].

28 Stromal Cells - Structure, Function, and Therapeutic Implications

2. Sources of stem cell

2.1. Embryonic stem cells

teratoma formation [5].

2.3. Fetal stem cells

2.4. Adult stem cells

3.1. History

3. Mesenchymal stem/stromal cells (MSCs)

2.2. Induced pluripotent stem cells

and differentiation capability [6].

The exact location of these cells in vivo is not known, but recent work suggests that MSCs are located in the perivascular spaces as sub-endothelial cells surrounding the vascular sinusoids in the bone marrow [23]. Bone marrow contains three main cell types: endothelial cells, hematopoietic stem cells, and stromal cells. Bone marrow connective tissue network is called the stroma. The stroma consists of a heterogeneous population of cells that provide structural and physiological microenvironment to support hematopoietic cells and forms a complex extracellular matrix, which supports the hematopoietic process [23]. However, the frequency of MSCs in human BM has been estimated to be in the range of 0.001–0.01% of the total nucleated cells. Furthermore, the frequency of MSCs declines with age, from 1/104 nucleated marrow cells in a newborn to about 1/10<sup>6</sup> nucleated marrow cells in an 80-year-old person [24].
