Original ResearchOpen Access
Directed differentiation protocols for successful human intestinal organoids derived from multiple induced pluripotent stem cell linesAmanda L Kauffman, Jason E Ekert, Alexandra V Gyurdieva, Michael A Rycyzyn, Pamela J Hornby
Applied Scientific Reports 2015 2 : 1 ( 23 February 2015 )
Therapeutic regeneration of molecularly engineered and transplanted autologous stem cells in neurological and cardiovascular diseases due to inability of self-regeneration or repair of endogenous stem cells at sites of inflammation or disease at various stages of progress for regeneration of the damaged tissue depending upon the sites and nature of degeneration.
Tumors contain a minority population of cancer stem cells that maintain the tumor. In marked contrast to the cancer stem cells, the tumor cells without "stemness" have either no capacity or a markedly diminished capacity, to form new tumors. Therefore, to treat cancer effectively, the cancer stem cell must be eliminated. The tumor will rapidly recur if the therapy eliminates cancer cells but spares a significant population of the cancer stem cells. Cancer stem cellsand their susceptibility over their expected to be "downstream or progeny" cancer cells represent a target for therapeutic interventions to prevent latency and consequently relapse or metastasis of the malignant disease. The tumor will rapidly recur if the therapy eliminates cancer cells but spares a significant population of the cancer stem cells.
Embryonic stem cells which are characteristic of totipotency differentiate into generations of the multiple organs. The totipotentstem cells differentiate further into pluripotency thatpopulate the organs with different sub-divisional components of the various individual organs. The pluripotent stem cells (eg. hematopoietic stem cells - blood, bone marrow and liver; cardiomyocytes - heart; hepatocytes - liver; neural stem cells - astrocytes, microglia and oligodendrocytes; mesenchymal stem cells - placenta) differentiate into multipotency as precursors to formation of the cellular components.
Retention of cellular phenotype is the hallmark of differentiation of pluripotent stem cells. Transcription factors and cellular signaling pathways play an important role in their self-renewal process.Self-renewal is abrogated when the terminal differentiation occurs. Maturation of the terminally differentiated cell loses the phenotype of the self-renewal antigen (eg. CD34-CD38- to CD34+CD38- to CD34+CD38+ to CD34-CD38+ to CD38+CD45+ to CD45+CDlin+).
Transient activation of CD4+ CD25+ T regulatory cells is required for autoimmune disease containment since their chronic activation leads to deleterious self-tolerance and infection or disease reactivation or tumour development as well as occurrences of relapse. On the other hand, elimination or escape of Treg cells also causes the reactivation and induction of tumors and relapse. Thus homeostasis of T regulatory cells is an overbearing requirement for prevention of autoimmune disorders arising from uncontrolled self-tolerance which also permits malignancies to occur. These CD4+ CD25+ T regulatory cells can be isolated from mesenchymal stem cells and CD34+ hematopoietic stem cells.
Autologous hematopoietic stem cell transplantation and reconstitution: Different species and including primates and humans for studies are being used for development, localization, and therapeutic strategies. Gene delivery through stem cells using specific viral vectors are also utilised to confer lineage specificity of transducedautologous or allogeneic stem cell gene expressionin the recipient while addressing graft versus host disease.
Inhibition of hematopoiesis results in reduced populations of blood forming cells. These also include thrombocytopenia (megakaryocytes and platelets), neutropenia (neutrophils), anemia (erythrocytes-hematocrit), granulocytopenia (granulocyte-macrophages). Decreased levels of T and B cells could also occur. This reduced differentiation of CD34+ hematopoietic progenitor stem cells could occur due to both infectious and non-communicable diseases and also due to their drug induced treatments.
Glaucoma is a common example of such nerve cell loss for Optic Nerve Degeneration due to increased intra-ocular pressure. Retinal degeneration is another example of eye related illnesses. The best hope for regeneration of these permanently damaged cells is optic stem cell therapy combined with continued drug treatments or other exogenous biomaterial implants depending upon the relevant ophthalmological condition.
Alzheimer's disease is a classic example of one suchconditions which results in excruciating memory loss. This gradually or rapidly degenerative condition requires imminent interventions through neural stem cell treatments.
This uncontrolled and deregulated blood cell proliferation is a frightening illness affecting individuals of all ages in a sudden manner. Autologous bone marrow transplantation is currently the best available option to treat such conditions. Bone marrow transplantation necessarily involves CD34+ hematopoietic progenitor stem cells.