answer the following question.
state the uses of stem cells with reference to a regenerative therapy and organ transplantation.
Answers
Stem cells are undifferentiated cells found in the body which have the ability to continuously divide, self-renew themselves and differentiate into various kinds of cells. With the capability of self-renewal, pluripotency and differentiation, stem cells have been believed to be useful for treatment of a wide variety of diseases in the future, including stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, spinal cord injury, baldness, blindness, deafness, wound healing, amyotrophic lateral-sclerosis, myocardial infarction, muscular dystrophy, osteoarthritis rheumatoid arthritis, Crohn’s disease, and diabetes. Amongst the applications, a number of adult stem cell therapies have already been practiced clinically. As an example, hematopoietic stem cell transplantation has been successfully applied to treat leukemia.
In addition to cell replacement therapy using stem cells, organ transplantation has been successfully practiced in clinics for organ failure of the liver or kidney. However, the severe shortage of donor organs has become the main obstacle to expand the organ transplant program. Generation of biological or semi-biological organs could be an alternative approach to solve the problem of the donor organ shortage. Notably, researchers have been hunting for ways to establish a whole organ using stem cells.
In recent years encouraging approaches for functional organ generation have emerged. The present manuscript provides an overview of organ generation using a single adult tissue stem cell, a blastocyst complementation system coupled with a specific stem cell niche, a method of decellularization and recellularization of bio-scaffold, and a combinatorial approach of tissue engineering and stem cells.
Generation of a functional organ from a single adult tissue stem cell
To demonstrate whether there are true stem cells in a given tissue, one needs to show that a single stem cell purified from the tissue has the capability of generating the entire organ. Up to present, it has been elegantly shown by independent groups that the mammary gland and the prostate can be generated in vivo from a single adult tissue stem cell [1, 2, 3].
Two laboratories have reported independently that single stem cells isolated from adult mouse mammary glands are able to produce secretory mammary glands when they are transplanted in the fat-pad in mice [1, 2]. It is long believed that there are stem cells in the mammary glands because this organ has the capability of undergoing an extensive growth at puberty and a second phase of expansion and retraction during pregnancy under the regulation of estrogen [4]. However, due to the lack of defined markers, there has been no reliable method to isolate mammary stem cells. This hypothesis was not proven until the work by the two groups. Based on some previous work by Clark and colleague [5], Shackleton et al. isolated putative mouse mammary stem cells using specific cell-surface markers (Lin-, CD29hi, CD24+) by FACS. They demonstrated these Lin-CD29hiCD24+ mammary cells have in vitro sphere formation capability and the ability to repopulate all mammary epithelial cells after transplantation into the fat-pad. Importantly, the investigators employed a lineage-tracer in the stem cells so to follow their ultimate phenotypes in vivo. They showed elegantly that a single cell within the Lin-CD29hiCD24+ population of the mouse mammary gland, marked with a LacZ report transgene, can reconstitute a completely functional mammary gland in vivo. Notably, the transplanted cell contributes to both the luminal and myoepithelial lineages and generates milk-producing lobuloalveolar units during pregnancy. This is the first report to demonstrate that a single adult tissue stem cell has multi-lineage differentiation capacity to produce a functional organ in an in vivo setting.
Similarly, using a colony-formation in vivo assay and an in vivo renal capsule transplantation approach, Gao and his colleagues have also reported that a single stem cell isolated from the adult mouse prostate epithelium has the capacity to generate a functional prostate [3]. Actually, prostate stem cells were postulated to exist because of its regenerative feature following androgen deprivation and replacement more than twenty years ago [6]. Because cell death mainly occurs in the luminal cell compartment after castration and cell proliferation mainly happens in the basal compartment following androgen replacement, stem cells are generally believed to reside in basal cell compartment and are able to repopulate the entire prostate epithelial cells.
A worldwide shortage of organs for clinical implantation establishes the need to bring forward and test new technologies that will help in solving the problem. The concepts of regenerative medicine hold the potential for augmenting organ function or repairing damaged organ or allowing regeneration of deteriorated organs and tissue. Researchers are exploring possible regenerative medicine applications in organ transplantation so that coming together of the two fields can benefit each other.