Stem Cells Self-Renewal
At the single-cell level, stem cells self-renew into more stem cells and give rise to progeny that differentiate into functional cells carrying out specific functions. Progenitor cells can be multipotent, oligopotent, or unipotent yet lack self-renewal capabilities. Hematopoietic stem cells are cells that give rise to more Hematopoietic stem cells and form all elements of the blood. Hematopoietic stem cells are entirely responsible for the development, maintenance, and regeneration of blood-forming tissues for life, and are the most important, if not the only cells required for successful engraftment in hematopoietic transplants.
Stem Cells gives rise to Lifelong Hematopoiesis
When transplanted at the single-cell level into irradiated mice, KTLS Hematopoietic stem cell gave rise to lifelong hematopoiesis, including a steady state of thousands of Hematopoietic stem cell with more than 10 blood cells produced daily.28–30 In humans the combination of positive selection for CD34, Thy-1, and negative selection for lineage markers, identified a homologous Hematopoietic stem cells population.
Following the success in rodent models, purified populations of human Hematopoietic stem cell were tested in three separate clinical trials of patients with myeloma, non-Hodgkin lymphoma, and metastatic breast cancer.
The Goal of Stem Cells Renewal
The goal was to purify Hematopoietic stem cell and thereby reduce the risk of occult malignant cells as a significant percentage of marrow or blood mononuclear cells are contaminated with malignant cells in all three diseases. These trials presented technical challenges primarily because of the rarity of Hematopoietic stem cell in marrow and granulocyte colony-stimulating factor (G-CSF) mobilized blood; however, adequate numbers of Hematopoietic stem cells could be isolated which were tumor free, from the majority of patients. The time to neutrophil and platelet recovery following purified Hematopoietic stem cell infusion was comparable to engraftment times using unmanipulated marrow as a graft source, yet there was a significant delay in T-cell recovery, especially of CD4+ T cells, of up to 6 months in almost all patients.
Possible side effects of Stem Cells Reconstruction
A number of patients developed unusual infections (i.e., severe cases of influenza, respiratory syncytial virus, cytomegalovirus and Pneumocystis pneumonia), thus, raising caution of using a “pure” Hematopoietic stem cell product as the sole source of hematopoietic reconstitution in clinical transplantation. Although too few patients were transplanted to evaluate whether the infusion of a product free of contaminating tumor cells impacted outcomes on event-free and overall survival, results appeared favorable.