Analysing The Regeneration Of Tissues Biology Essay

Published: Last Edited:

This essay has been submitted by a student. This is not an example of the work written by our professional essay writers.

Regeneration is a remarkable physiological process in which remaining tissues organize to reform a missing body part. Several invertebrates, such as planarian, flatworms and Hydra, regenerate tissues with speed and precision. From vertebrates, the salamanders, repair lost body parts through the dedifferentiation of specialized cells into new precursor cells. Stem cells can also be identified in plants in the root and shoot meristems (Bangso and Richard, 2004). However, the majority of higher vertebrates are incapable of any form of whole-organ regeneration, even though they had all the necessary instructions and machinery to generate the tissue during embryonic development (Andrews, 2002).

The canonical definition of a stem cell is a cell with the ability to divide indefinitely in culture and with the potential to give rise to mature specialized cell types (Alison et al., 2002) . This style of cell division characteristic of stem cells is asymmetric. In fact, when a stem cell divides, the daughter cells can either enter a path leading to the formation of a differentiated specialized cell or self-renew to remain a stem cell, thereby ensuring that a pool of stem cells is constantly replenished in the adult organ. This mechanism is a necessary physiological mechanism for the maintenance of the cellular composition of tissues and organs in the body (Andrews, 2002; Bangso and Richard, 2004; Kanatsu-Shinohara et al., 2004) .

The field of stem cells began with the study of teratocarcinomas in the 1960s. Teratocarcinomas are malignant germ cell tumors that form an undifferentiated EC (Embryonal Carcinoma cells) component and a differentiated component that can include all three germ layers. Mouse EC cell lines that could be stably propagated in vitro were established in the early 1970s. They could be cultured in sufficient quantities to perform experiments that would have been impossible with intact mammalian embryos. (Kahan and Ephrussi, 1970) .

Isolation of a Pluripotent cell line from early mouse embryos cultured in a medium conditioned by teratocarcinomas stem cells was done in 1981 in following of previous researches (Evans and Kaufman, 1981; Martin, 1981). After that derivation of human embryonic stem cells (ESCs) in 1998 ignited an explosion of public interest in stem cells (Thamson et al., 1998) . In turn, the recent derivation of mouse and human induced pluripotent stem cells depended on the prior studies on mouse and human ESCs. Both human ESCs and induced pluripotent stem cells can self-renew indefinitely in vitro while maintaining the ability to differentiate into advanced derivatives of all three germ layers, features very useful for understanding the differentiation and function of human tissues, for drug screen and toxicity testing, and for cellular transplantation therapies (James et al., 2008) . Clearly, stem cell research leading to prospective therapies in reparative medicine has the potential to affect the lives of millions of people around the world for the better and there is good reason to be optimistic.

Types of stem cells and its application:

Stem cells can be classified as Totipotent, Pluripotent and Multipotent cells. Totipotency is the ability to form all cell types of the conceptus, including the entire fetus and placenta. These cells have unlimited capability; they can basically form the whole organism. Early mammalian embryos are clusters of totipotent cells.

Pluripotency is the ability to form several cell types of all three germ layers (ectoderm, mesoderm and endoderm) but not the whole organism. In theory, pluripotent stem cells have the ability to form all the 200 or so cell types in the body.

Multipotency is the ability of giving rise to a limited range of cells and tissues appropriate to their location.

There are four classes of pluripotent stem cells: A) Embryonic stem cells, B) Embryonic germ cells, C) Multipotent germline stem cells or mGSCs, D) Embryonic carcinoma cells, E) The Multipotent adult progenitor cell from bone marrow.

Mammalian development starts from a single cell that can give rise to all cells required for a new life, but through subsequent differentiation events, developmental potential becomes increasingly restricted. As the one-cell embryo divides, it forms a morula, a "mulberry"-like cluster of undifferentiated cells. The first differentiation event occurs when the outer layer of cells of the morula differentiates to the trophectoderm, forming the blastocyst stage embryo. The cells inside the blastocyst (inner cell mass, or ICM) give rise to all cells of the adult body and some extraembryonic tissues, while the trophectoderm gives rise to the outer layer of the placenta (Andrews, 2002; Bangso and Richard, 2004; James et al., 2008) .

Embryonic stem (ES) cells, however, are derived from the isolated inner cell masses (ICM) of mammalian. The continuous in vitro subculture and expansion of an isolated ICM on an embryonic fibroblast feeder layer (human or murine) leads to the development of an embryonic stem cell line. In nature, however, embryonic stem cells are ephemeral and present only in the ICM of blastocysts. These cells are destined to differentiate into tissues of the three primordial germ layers (ectoderm, mesoderm and endoderm) and finally form the adult organism (Bangso and Richard, 2004).

Totally, if early mouse embryos are transferred to extrauterine sites, such as the kidney or testis capsules of adult mice, they can develop into teratocarcinomas (Solter and Knowles, 1978) . These embryo transplantation experiments demonstrated that the intact embryo has a cell population that can give rise to pluripotent stem cell lines, and this key discovery led to the search for culture conditions that would allow the direct in vitro derivation of pluripotent stem cells from the embryo, without the intermediate need for teratocarcinoma formation in vivo.

Embryonic germ (EG) cells are isolated from primordial germ cells (PGCs) during the developing gonadal ridge of 5 to 9 week-old fetuses of elective abortions. These cells are diploid germ cell precursors that transiently exist in the embryo before they enter into close association with the somatic cells of the gonad and become irreversibly committed as germ cells (Anway et al., 2003) .

Primordial germ cells are pluripotent and are capable of forming all three primordial germ layers. The derivation of EG cells was reported in 1998 , but in spite of efforts by several groups, their long-term proliferative potential appears to be limited (Bangso and Richard, 2004; Shamblott et al., 1998). Unlike ES cells, however, EG cells retain some features of the original PGCs, including genome-wide demethylation, erasure of genomic imprints, and reactivation of X-chromosomes , the degree of which likely reflects the developmental stages of the PGCs from which they are derived (James et al., 2008; Maser and DePinho, 2002) .

Other Pluripotent stem cells are multipotent germline stem cells (mGSCs) that more recently have been derived from both neonatal and adult mouse testis. These cells share a similar morphology with mouse ES cells, express typical mouse ES cell specific markers, differentiate into multiple lineages in vitro, form teratomas, and contribute extensively to chimeras including germline cells upon injection into blastocysts. However, mGSCs have an epigenetic status distinct from both ES cells and germline stem cells. The mouse testis contains different subpopulations of germline stem cells. The origin of mGSCs is still somewhat unclear, though it might be possible that in vitro culture of germline stem cells reprograms a minority of these cells to resume an ES cell-like state(Guan et al., 2006; Izadyar et al., 2008; Kanatsu-Shinohara et al., 2004) .

Another type of Pluripoten stem cells is Embryonal Carcinoma cell (ECs). Kleinsmith and Pierce demonstrated that a single EC cell is capable of both unlimited self-renewal and multi lineage differentiation, establishing the existence of a pluripotent stem cell and also providing the intellectual framework for both mouse and human embryonic stem (ES) cells. This was also the first experimental demonstration of a cancer stem cell, predating the current intense interest in cancer stem cells by several decades(James et al., 2008; Kleinsmith and Pierce Jr., 1964) . EC cells express antigens and proteins that are similar to cells present in the ICM, which led to the concept that EC cells are an in vitro counterpart of the pluripotent cells present in the ICM. Indeed, some EC cell lines are able to contribute to various somatic cell types upon injection into mouse blastocysts. However, most EC cell lines have limited developmental potential and contribute poorly to chimeric mice, likely due to the accumulation of genetic changes during teratocarcinoma formation and growth(Gachelin, 1977; Solter and Knowles, 1978) .

Human embryonal carcinoma (hEC) cell lines have identified from tumours of germ cell origin at the first time. These cells have long served as the human counterpart of murine EC cells for studying human development and differentiation in vitro (Andrews, 2002) . Cell lines of hEC are capable of multi lineage differentiation in vitro but, being of tumour origin, are unfortunately mostly aneuploid, which makes them unsuitable for cell-replacement therapeutics. in contrast to mouse EC cells, human EC cells are highly aneuploid, which likely accounts for their inability to differentiate into a wide range of somatic cell types, and which limits their utility as an in vitro model of human development (James et al., 2008).

A highly plastic, adult-derived bone marrow cell, with features very similar to mesenchymal stem cells (MSC) has also been described as a Multipotent Adult Progenitor Cell (MAPC) (Jiang et al., 2002) . These cells are initially isolated together with MSC, but subsequently grow indefinitely in nutrient-poor medium. In specific conditioning media, MAPC can differentiate into cells which express markers of endodermal, mesodermal, and ectodermal origin. The same pluripotent ability can be observed in vivo when MAPC are injected into murine blastocysts or when MAPC are injected intravenously into sublethally-irradiated immunodeficient mice. The relationship of MAPC to MSC is unknown. MAPC could be MSC progenitors or may even represent a cell population generated in vitro as an artifact which has no counterpart in vivo (Dazzi et al., 2006).

Multipotency is seen in adult stem cells for example blood stem cells give rise to red blood cells, white blood cells and platelets, whereas skin stem cells give rise to the various types of skin cells. Adult stem cells-also known as somatic stem cells-can be found in diverse tissues and organs. The best-studied adult stem cell is the hematopoietic stem cell (HSC). These cells have been used widely in clinical settings for over 40 years and form the basis of bone marrow transplantation successfully. Unfortunately, HSCs-like many other adult stem cells-are rare and difficult to isolate in large numbers from their in vivo niche (Igura et al., 2004) .

Adult stem cells have also been isolated from several other organs such as the brain (neuronal stem cells), skin (epidermal stem cells), eye (retinal stem cells) and gut (intestinal crypt stem cells). Mesenchymal stem cells (MSCs) are another well characterized population of adult stem cells.

Some recent reports suggest that adult stem cells, such as haemopoietic stem cells, neuronal stem cells and mesenchymal stem cells, could cross boundaries and differentiate into cells of a different tissue. This phenomenon of unprecedented adult stem cell plasticity has been termed 'transdifferentiation' and appears to defy canonical embryological rules of strict lineage commitment during embryonic development(Bjornson et al., 1999; Krause et al., 2001) .