Human adult stem cells, which are scarce in various tissues, secure processes of tissue renewal and regeneration. Bone marrow (BM) contains hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), both responsible for the generation of the BM microenvironment. Adult MSC isolated from BM, liver, and heart, can be induced to proliferate extensively in vitro, and their progeny retains clonogenicity. In addition, these cells, unlike HSC, can be pushed by cytokines to express features that in vivo are associated with derivatives of the 3 germ layers. Yet, such transgermal, multilineage differentiation potential of MSCs proved in vitro, requires in vivo validation to confirm survival and self-renewal ability after transplantation, without the loss of properties acquired ex vivo. The existing differentiated cells in tissue microenvironment strictly limit the expansion of stem cells and affect the direction of differentiation of stem cell progeny. The so-called induced pluripotent cells (iPCs) may be generated from human adult skin cells that had been reprogrammed to an undifferentiated state by inserting just four genes. The iPCs differentiate in vitro into the cell types of 3 germ layers, and in vivo into teratomas. Success in reprogramming of adult fibroblasts into cells with embryonic stem cell capability to become any cell type in the body, could bypass ethical controversies surrounding the use of human embryos or oocytes. However, before the iPCs can be introduced in the clinic, additional effort is required to avoid employing vectors that integrate into the genome, and oncogenes, for turning back the developmental clock. With the presently used techniques, skin cells reprogrammed into iPCs carry multiple copies of the retroviruses used to insert the genes, what can lead to mutations at the insertion site, and may cause tumors. Human iPCs with retroviral integration are potentially useful for studying disease mechanisms and for drug screening. Once the safety issue is overcome, iPCs will be applicable in regenerative medicine. So far, the most advanced application of stem cells in medicine is hematopoietic stem-cell transplantation (HSCT) in cancer patients and in patients with nonmalignant hematologic disorders. Chemotherapy (CHT) is a double edge-sword that eliminates cancer cells at the price of hematologic toxicity. In addition, many cancers arise from rare self-renewing cells (cancer stem cells) that acquired oncogenic mutations at the stage preceding differentiation. Cancer stem cells being biologically distinct from their more numerous differentiated progeny may be resistant to treatment designed to target differentiated cells. Then, dramatic response of the bulk of cancer for treatment targeting differentiated cells is followed by the re-growth of cancer originating from cancer stem cell reservoir. High-dose CHT potentially improves targeting a reservoir of cancer stem cells, but seriously increases morbidity due to the delay or lack of hematologic recovery. Infusion of autologous or allogeneic HSCs following high-dose CHT, secures hematologic recovery. Allogeneic HSCT may also produce immune-mediated graft-versus-tumor reaction that eradicates cancer. However, allogeneic HSCT is associated with a risk of graft-versus-host disease (GvHD), which is increased for transplants from HLA-disparate relatives. Co-transplantation of ex vivo expanded donor MSCs reduces the risk of graft failure in haploidentical HSCT. MSCs inhibit alloreactive T cells, induce dendritic cells (DCs) to tolerogenic function and stimulate proliferation of regulatory T cells. An alternative approach, currently examined in pre-clinical studies, is based on the administration of tolerogenic DCs or regulatory T cells to prevent or to treat posttransplantational GvHD. DCs generated from HSCs ex vivo by stimulation with cytokines have already been used as a natural adjuvant in clinical studies on anti-cancer vaccines.

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