Stem cells are generally undifferentiated cells that are commonly found in all organisms that are multi cellular. The cells have this unique ability to constantly repeat themselves through the process of repeating mitotic cell division and differentiation. The room finally give rise to a wide, diverse range of other specialized cells that are entirely different from the first cell type. The pioneers of this research in the stem cell scope are James E. Till and A. McCulloch who carried out their experiments at the University of Toronto in the years 1960 -1970.
There are two main different types of stem cells in different mammalian bodies. The two are one, the embryonic stem cells found in the inner cell wall of a blast cyst. These cells are highly mitotic, and the stem cells eventually separate and specialize into the fetal tissues when the blast cyst develops into an embryo. The second stem cells is the adult stem cells that are now found in the tissues of adult organisms. These stem cells are hugely beneficial as they act as a repair system for the body when certain tissues wear off. They have the authority to restore specialized cells in the area and also keep in practice the number and position of regenerative body organs. Examples of these organs are the skin and blood. Stem cell therapy is a hugely significant aspect of treatment in the modern world as it has been used in the study of human diseases. A clear example is bone marrow transplants used to treat blood cancer or leukemia, a defect in which the body is unable to provide individual components in stock. This treatment has also been used in cloning and genetic Engineering in the developed nations of the world.
What is a stem cell niche?
Stem cell function refers to the microenvironment that certain stem cells are found or located. The stem cells are usually directed or signaled by the micro environment in which they settle on what action to take, either promote self regeneration to make other like cells or differentiate and specialize to form different tissues. Stem cell populations are established and located in niches that are locations that manage and control how the stem cells in their position will help in the maintenance, repair and regeneration of body tissues. The niches are hugely valuable as they protect the body host from the danger of over exuberant proliferation of the stem cells. The niche also protects the individual stem cells from the danger of depletion due to overuse and misuse. The niche acts as an intermediate between the organism and the stem cells by integrating signals that direct the conduct of the stem cells in response to requirements of the organism. It is said that the niche help the organism and stem cells communicate and strike a balance. This communication establishes the dynamic and automated system required for sustaining normal bodily and tissue functions and the end of stem cell therapeutics.
The epithelial stem cell niche is found in the hair follicle bulge. This is a member of the outer root sheath and continues with the sebaceous gland and the inter follicular epidermis. This hair follicles continuously go through a cycle of growth, rest and re growth stages. It had been stipulated that the stem cells located deep in the follicle bulge were solely responsible for the growth of hair. In short, bulge cells were said to be hair follicle stem cells because of the strategic location and quiescent nature. Further investigations showed that the bulge cells were responsible for the rise and progress of the epithelial cells in the regenerating secondary follicle during the growth stage also called anagen. The group are also contributors to the overlying epidermis and the sebaceous gland. Recently researchers showed that the bulge cells can maintain their ability to generate new hair follicle cells once they are removed from their niche. This was made possible by the identification of the bulge cell markers, CD34 and cytokeratin promoter activity. However, the stem cells were only able to do this when the cells were combined with dermal cells to encourage the active taken from the dermis layer of the skin. Inter follicular epidermal cells also retain some limited capacity to produce other hair follicle cells even after separation. However, the efficiency of the bulge cells in this renewal of cell is much higher than that of these epidermal cells. In addition to that, many other types of stem cells have shown considerable ability to produce the hair follicle cells. The examples include, embryonic stem cells, neural stem cells and bone marrow stem cells. Thus, it can only be deduced that stem cells are highly flexible. Even others that are found or located elsewhere and not in the hair follicle niche can still be used to generate hair development if they are given the proper signals. The stem cells in hair follicles can also be used to generate the performance of other tissues if they are exposed to the correct signals.
The role of protein noggin
Noggin is one of the proteins found in the hair follicle and is a significant enemy of proteins 4and 2 (BMP 2 And 4) that are bone morphonegic and are members of the TGF and BMP super family. The protein Noggin binds Bmp 2 and 4 with harmony and prevents their interaction with BMP receptors. It plays critical roles in controlling morphogenesis of ecto dermal derivatives and in regulating the apoptosis during hair follicle development. The protein also stimulates morphogenesis of ecto dermal derivatives and downgrades BMP mediated apoptosis. Noggin plays a singularly crucial role during the initiation and establishment of any new hair growth signal. This applies in the postnatal skin and in the new apoptosis driven regression of the hair follicle in both normal skin and in skin that is in any way affected by alopecia areata. During the postnatal development, of the hair follicle it shows cyclic life with in between and varied periods of relative resting, active and continuous development then finally regression. Initiation of any new hair period of growth in postnatal skin requires thorough and complete neutralization of the inhibitory activity created by the presence of bone morphogenetic protein 4 (BMP4) by the BMP antagonist protein noggin. When the hair follicle is in a level of rest, BMP4 RAN predominates over the protein noggin in the epithelium and mesenchyme . Anagen ( resting phase) site is followed by over-regulating of the BMP4 and increased noggin mRNA in the hair follicle. In addition, the provision of noggin protein induces selective capture of the resting state growth in the non-tylotrich hair follicle. As a hair growth inducer, the protein noggin increases Shh mRNA in the hair follicle whereas BMP4 down regulates Shh. This conclusion suggests and proves that modulation of BMP4 signaling by protein noggin is necessary and supremely beneficial in the hair grow phase induction in postnatal skin. The cyclic activity of the hair follicle is governed by the epithelial - mesenchyme interactions between hair follicles keratinocytes and fibroblasts of the dermal papilla. The hair follicle development between the different hair follicle stages in its growth is regulated and guided by a tightly controlled balance between several development stimulatory and inhibitory factors.
The hair follicle development from the stage of telogen to the stage of anagen is a solitary system of publication regeneration. This is characterized by a sudden activation of cell proliferation in the secondary hair germ and bulge also called the proximal follicular epithelium. The result of this is the violation of the elongating hair follicle into the near by the subcutaneous tissue and is accompanied by the construction of the hair matrix and inner sheath of the root hair. In addition of this, there is the distinction of melanocyte precursors that ultimately lead to melanogenesis. The full restoration of the hair fiber producing unit is typically associated with the formation of the epithelial hair bulb. This is thebulb thhat is surrounding the dermal papilla located deep in the subcutaneous tissue.
The induction of cell proliferation in the germinative compartment of the telogen hair follicle leading to anagen development can be induced in an experiment by use of mechanical or chemical stimuli. An example is the mechanical removal of the hair shaft also called depletion induces the onset of the resting period in mice and humans. Abnormal shedding of hair in mouse mutants that have constitutive deletion of the adhesion molecule also induces the process of anagen. The deletion of STAT3 transcription factor is profoundly associated with a long - time stay of the hair follicles in telogen. The chemical stimulation of a wide range of molecular path ways results in the induction of anagen. These experiments are used to show that the local stability of hair growth stimulators and inhibitors in the proximal part of the hair follicle involving the bulge, secondary hair germ, dermal papilla is exceedingly serious and useful in the initiation of a new hair growth wave.
As hair follicle and the development of anagen both have many similarities and result in the construction of the hair bulb that produces the bulb. It was stipulated for a long time that both of the processes are regulated by similar mechanisms. It has been proven and demonstrated that increased intra dermal expression of Shh stimulates the transformation of the hair follicle from telogen phase to anagen phase. Thus, Shh blockade by neutralizing antibody alters the transition of the hair follicle from telogen moment to anagen stage in the postnatal skin. Bone morphogenetic proteins 2 and 4( BMP2/4) have an inhibiting effect on the induction of several ecto dermal derivatives, for example, the neural tube, tooth, or feather during embryogenesis.
To conduct the experiments, eight week old female mice were purchased to be used to determine noggin expression in postnatal spontaneously cycling hair follicle by histoenzymatic staining cryosections with galactosidase. All the mice present were feed on water and murine chow plus put under 12 hour light cycles. Active hair grown (anagen) was induced in the back skin during the telogen stage of the cycle of the hair follicle by applying wax rosin mix with subsequent depletion. Hair follicle telogen anagen transformation was carefully studied using four of the eight mice per time. The neck skin was harvested parallel to the vertebral column and was embedded for obtaining longitudinal cryosections. Semi quantitative RT - PCR analysis of proteins noggin, BMP4, BMPR IA. Total RNA was isolated from the full thickness back skin samples of the mice harvested at telogen, early anagen, and late anagen stages of the hair cycle. The skin was homogenized in liquid nitrogen using a mortar and total RNA was isolated. Protein noggin was isolated from the supernatant of noggin producing CHO B3.A4 cells. Beads were then injected into the back skin of mice, with all the hair follicle in it's resting stage. Skin was harvested on days 5 - 18 after implantation. In the skin samples treated by noggin, the percentage of hair follicle at the different hair cycle stages was assessed and defined on the basis of accepted morphological criteria. To determine the defined sub stages of hair run as precisely as possible, the histo chemical identification of endogenous alkaline phosphate activity was used, as this highlights the dermal papilla as a convenient morphological marker for staging hair follicle anagen development.
This test is used to verify that hair growth phase induction in postnatal skin is associated with up regulation of protein noggin. By the use, of quantitative RT - PCR, high steady, state of Noggin were found in telogen skin, whereas extraordinarily minimal levels of noggin were found. Hair follicle development from telogen to previous anagen was associated with significant up regulation of sound levels of protein noggin. In other results, steady state levels of noggin in anagen remained as high as in the telogen shape and were in any way significantly.