Natural killer (NK) cells and natural killer T (NKT) cells are subsets of lymphocytes that share some phenotypical and functional similarities. Both cell types can rapidly respond to the presence of tumour cells and participate in antitumour immune responses. This has prompted interest in the development of innovative cancer therapies that are based on the manipulation of NK and NKT cells. Recent studies have highlighted how the immune reactivity of NK and NKT cells is shaped by the environment in which they develop. The rational use of these cells in cancer immunotherapies awaits a better understanding of their effector functions, migratory patterns and survival properties in humans.

Targeting natural killer cells and natural killer T cells in cancer.

Mesenchymal stem cells (MSC) have generated a great amount of enthusiasm over the past decade as a novel therapeutic paradigm for a variety of diseases. Currently, MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy. This review provides an overview of the recent clinical findings related to MSC therapeutic effects. Roles of MSCs in clinical trials conducted to treat graft-versus-host-disease (GVHD) and cardiovascular diseases are highlighted. Clinical application of MSC are mainly attributed to their important four biological properties- the ability to home to sites of inflammation following tissue injury when injected intravenously; to differentiate into various cell types; to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation and to perform immunomodulatory functions. Here, we will discuss these four properties. Moreover, the issues surrounding clinical grade MSCs and principles for MSC therapeutic approaches are also addressed on the transition of MSCs therapy from bench side to bedside.

/pdf/clinical-applications-of-mesenchymal-stem-cells-3v536s3k40.pdf

Clinical applications of mesenchymal stem cells

http://incan-mexico.org/wp_hematologia/wp-content/uploads/Fuentes-del-trasplante.pdf

Hematopoietic stem cell transplantation donor sources in the 21st century: choosing the ideal donor when a perfect match does not exist.

Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients

Background: One of the greatest challenges for medicine is to find a safe and effective treatment for immune-related diseases. However, due to the low efficacy of the treatment available and the occurrence of serious adverse effects, many groups are currently searching for alternatives to the traditional therapy. In this regard, the use of human mesenchymal stem cells (hMSCs) represents a great promise for the treatment of a variety of immune-related diseases due to their potent immunomodulatory properties. The main objective of this study is, therefore, to present and summarize, through a systematic review of the literature, in vivo studies in which the efficacy of the administration of hMSCs for the treatment of immune-related diseases was evaluated. Methods: The article search was conducted in PubMed/MEDLINE, Scopus and Web of Science databases. Original research articles assessing the therapeutic potential of hMSCs administration for the in vivo treatment immune-related diseases, published from 1984 to December 2017, were selected and evaluated. Results: A total of 132 manuscripts formed the basis of this systematic review. Most of the studies analyzed reported positive results after hMSCs administration. Clinical effects commonly observed include an increase in the survival rates and a reduction in the severity and incidence of the immune-related diseases studied. In addition, hMSCs administration resulted in an inhibition in the proliferation and activation of CD19+ B cells, CD4+ Th1 and Th17 cells, CD8+ T cells, NK cells, macrophages, monocytes, and neutrophils. The clonal expansion of both Bregs and Tregs cells, however, was stimulated. Administration of hMSCs also resulted in a reduction in the levels of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL-1, IL-2, IL-12, and IL-17 and in an increase in the levels of immunoregulatory cytokines such as IL-4, IL-10, and IL-13. Conclusions: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.

/pdf/the-use-of-human-mesenchymal-stem-cells-as-therapeutic-2pq2a66fpm.pdf

The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

A modified haploidentical nonmyeloablative transplantation without T cell depletion for high-risk acute leukemia: successful engraftment and mild GVHD.

This study was purposed to investigate the reconstitution of immune system in patients with acute lymphocyte leukemia (ALL) or acute myeloid leukemia (AML) after HLA-mismatched nonmyeloablative hematopoietic stem cell transplantation (NHSCT) and its relation with infection and GVHD. 6 ALL and 4 AML patients having HLA-mismatched related donors received the nonmyeloablative precondition regimen composed of fludarabine (Fln), ATG, Ara-C, CTX and total body irradiation (TBI) in dose 2 Gy. The GVHD was prevented and treated by CsA, anti-CD25 antibody and mycophenolic mofetil (MMF) before and after transplantation. The flow cytometry was used to detect the changes of total T cells, help/inducer T cells, suppressor/killer T cells, gamma/delta T cells, B cells, NK cells, NKT cells, regulatory T cells, activated T cells, naive T cells, memory T cells and ratio of CD4/CD8 in patients with remission resulting from chemotherapy before transplantation, and analyse the relation of immunofunctional cells to infection and GVHD after transplantation, compare the difference in recovery of immune system of ALL and AML patients. The results showed that the recovery of total lymphocytes and lymphocyte subsets displayed one's own regular pattern. As compared with patients without GVHD, the counts of lymphocyte subsets in patients with GVHD was higher, while the counts of gamma/delta T cells, regulatory T cells, NK cells, the counts of B cells, NK cells, naive cells and CD4/CD8 ratio as well as the counts of B cells, naive T cells and NK cells were lower at 1 month, 2 - 3 months and 6 - 8 months after transplantation respectively. The total T cells and subsets recovered slowly, but NK cells and NKT cells recovered rapidly in patients with infection at early period after transplantation, the B cells and naive B cells recovered rapidly at 3 months after transplantation. There was no difference in lymphocyte recovery between ALL and AML patients. It is concluded that the analysis of each lymphocyte subsets may indirectly show the recovery of thymus function in patients, the changes of NK cells, B cells and naive T cells have an important significance for identifying and forecasting the GVHD and infection.

[Changes of lymphocyte subsets in acute leukemia patients after HLA-mismatched nonmyeloablative hematopoietic stem cell transplantation].

Wei L, Zuo H, Sun X, Liu T, Guo M, Liu G, Sun Q, Qiao J, Wang D, Yu C, Hu K, Dong Z, Ai H. WT1-specific CTL cells of recipient origin may exist in the peripheral blood of patients achieving full donor chimerism soon after nonmyeloablative transplantation. Clin Transplant 2011: 25: 689–696. © 2011 John Wiley & Sons A/S.



Abstract:  This study was performed to assay whether leukemia-associated antigen (LAA)-specific CTLs of recipient origin existed in the blood of patients who achieved full donor chimerism (FDC) soon after nonmyeloablative transplantation (NST). In 15 patients who received haplo-identical NST, WT1+CD8+CTLs were detected with WT1/HLA-A*0201 pentamer, and the donor–recipient chimerism levels were analyzed by three methods. Results showed that WT1+CD8+CTLs could be detected in patients with HLA-A*0201 expressing only in recipient, and cells of recipient origin existed in the blood of patients who achieved FDC, which suggested that LAA-specific CTLs of recipient origin may exist in patients achieving FDC soon after NST.

WT1-specific CTL cells of recipient origin may exist in the peripheral blood of patients achieving full donor chimerism soon after nonmyeloablative transplantation.

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Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients

A modified haploidentical nonmyeloablative transplantation without T cell depletion for high-risk acute leukemia: successful engraftment and mild GVHD.

[Changes of lymphocyte subsets in acute leukemia patients after HLA-mismatched nonmyeloablative hematopoietic stem cell transplantation].

WT1-specific CTL cells of recipient origin may exist in the peripheral blood of patients achieving full donor chimerism soon after nonmyeloablative transplantation.