Romero-Ramirez H.,CINVESTAV |
Morales-Guadarrama M.T.,CINVESTAV |
Pelayo R.,Oncology Hospital |
Immunology | Year: 2015
CD38 is a 45 000 molecular weight transmembrane protein that is expressed in immature and mature lymphocytes. However, the expression and function of CD38 during B-cell differentiation in mice is poorly understood. Here, we report that CD38 is expressed from the earliest stages of B-cell development. Pre-pro-B, pro-B, pre-B and immature B cells from murine bone marrow all stained positive for CD38. Interestingly, CD38 expression increases with B-cell maturation. To assess the role of CD38 during B-cell maturation, CD38-deficient mice were analysed. CD38-/- mice showed a significant increase in both the frequency of B-lineage cells and the absolute numbers of pre-pro-B cells in bone marrow; however, no other differences were observed at later stages. CD38 cross-linking in Ba/F3 cells promoted apoptosis and marked extracellular signal-regulated kinase (ERK) phosphorylation, and these effects were reduced by treatment with the mitogen-activated protein kinase/ERK kinase inhibitor PD98059, and similar effects were observed in B-cell precursors from bone marrow. These data demonstrate that B-cell precursors in mouse bone marrow express functional CD38 and implicate the early ligation of CD38 in the ERK-associated regulation of the B-lineage differentiation pathway. © 2014 John Wiley & Sons Ltd.
Flores-Guzman P.,Oncology Hospital |
Fernandez-Sanchez V.,Oncology Hospital |
Mayani H.,Oncology Hospital
Stem Cells Translational Medicine | Year: 2013
Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play key roles in the production of mature blood cells and in the biology and clinical outcomes of hematopoietic transplants. The numbers of these cells, however, are extremely low, particularly in umbilical cord blood (UCB); thus, ex vivo expansion of human UCB-derived HSCs and HPCs has become a priority in the biomedical field. Expansion of progenitor cells can be achieved by culturing such cells in the presence of different combinations of recombinant stimulatory cytokines; in contrast, expansion of actual HSCs has proved to be more difficult because, in addition to needing recombinant cytokines, HSCs seem to deeply depend on the presence of stromal cells and/or elements that promote the activation of particular self-renewal signaling pathways. Hence, there is still controversy regarding the optimal culture conditions that should be used to achieve this. To date, UCB transplants using ex vivo-expanded cells have already been performed for the treatment of different hematological disorders, and although results are still far from being optimal, the advances are encouraging. Recent studies suggest that HSCs may also give rise to nonhematopoietic cells, such as neural, cardiac, mesenchymal, and muscle cells. Such plasticity and the possibility of producing nonhematopoietic cells at the clinical scale could bring new alternatives for the treatment of neural, metabolic, orthopedic, cardiac, and neoplastic disorders. Once standardized, ex vivo expansion of human HSCs/HPCs will surely have a positive impact in regenerative medicine. © AlphaMed Press 2013.
Fajardo-Orduna G.R.,Oncology Hospital |
Mayani H.,Oncology Hospital |
Montesinos J.J.,Oncology Hospital
Archives of Medical Research | Year: 2015
Mesenchymal stem cells (MSCs) play an important role in the physiology and homeostasis of the hematopoietic system. Because MSCs generate most of the stromal cells present in the bone marrow (BM), form part of the hematopoietic stem cell (HSC) niche, and produce various molecules regulating hematopoiesis, their hematopoiesis-supporting capacity has been demonstrated. In the last decade, BM-MSCs have been proposed to be useful in some ex vivo protocols for HSC expansion, with the aim of expanding their numbers for transplant purposes (HSC transplant, HSCT). Furthermore, application of MSCs has been proposed as an adjuvant cellular therapy for promoting rapid hematopoietic recovery in HSCT patients. Although the MSCs used in preliminary clinical trials have come from the BM, isolation of MSCs from far more accessible sources such as neonatal tissues has now been achieved, and these cells have been found to possess similar biological characteristics to those isolated from the BM. Therefore, such tissues are now considered as a potential alternative source of MSCs for clinical applications. In this review, we discuss current knowledge regarding the biological characteristics of MSCs as related to their capacity to support the formation of hematopoietic stem and progenitor cells. We also describe MSC manipulation for ex vivo HSC expansion protocols used for transplants and their clinical relevance for hematopoietic recovery in HSCT patients. © 2015 IMSS.
Mayani H.,Oncology Hospital
Stem Cells and Development | Year: 2010
From the first studies performed by Broxmeyer and his group, in the late 1980s, evidence was presented indicating that hematopoietic progenitor cells from human umbilical cord blood (UCB) possessed certain in vitro biological features that differed from those observed in their adult counterparts. Throughout the past 20 years, these observations have been confirmed and expanded by several groups, using both in vitro and in vivo models. Today, it is widely recognized that stem and progenitor cells present in UCB are biologically different from those present in adult marrow or peripheral blood. As compared to cells from adult subjects, UCB-derived hematopoietic cells possess higher proliferation and expansion potentials, and their capacity to self-renew is also superior to that of adult cells. Although the mechanisms responsible for such biological differences are still not fully understood, telomere dynamics, cell cycle progression, certain transcription factor pathways, differential gene expression, and the autocrine production of particular cytokines are some of the mechanisms that have been implicated. Understanding, at the cellular and molecular levels, the biological differences between neonatal and adult hematopoietic cells has a 2-fold relevance. On the one hand, it will help to understand and characterize basic principles and mechanisms involved in human developmental biology; on the other hand, it will help to gain a deeper knowledge on the biology of hematopoietic cell transplants and to improve and optimize such a clinical procedure. © Mary Ann Liebert, Inc. 2010.
Aviles A.,Oncology Hospital |
Neri N.,Oncology Hospital |
Nambo M.-J.,Oncology Hospital
International Journal of Cancer | Year: 2012
Treatment of hematological malignancies (HM) during pregnancy remain unsolved, although the use of chemotherapy during second and third trimester has been accepted because of the low rate of toxicities, the use of cytotoxic drugs during first trimester is generally forbidden. Most of the concerns are related to congenital abnormalities and development, but long-term follow-up of these children are not available. From 1975 to 2008, we diagnosed and treated 15,750 cases of HM, and 143 female patients were pregnant during this time that were treated with combined chemotherapy. In our study, we present the long-term follow-up (the median follow-up was 22.4 years with a range of 3.8-32.0 years) of 54 newborns, whose mothers received chemotherapy during the first trimester of pregnancy with an intent-to-cure HM. Physical and neurological development were carefully assessed, and cardiac and chromosomal studies were performed until the age of 20 years to evaluate late toxicities. The obstetrical development of pregnancy was normal, chemotherapy was used at doses and schedules used in normal patients. Low-weight birth was the most frequent finding. No congenital abnormalities were detected. Physical, psychological and neurological developments were normal. Education and academic degree were according to the economical and social factors. Cardiac function and chromosomal examination were normal. No neoplasm or acute leukemia has been observed in these children. Forty-three mothers are alive and disease-free and can be considered cured. The use of cytotoxic drugs during the first trimester to treat HM seems to be beneficial to both the mother and fetus, and chemotherapy during the first trimester can be considered if the cure of the patient is the goal. Copyright © 2012 UICC.
Aviles A.,Oncology Research Oncology Diseases |
Jesus Nambo M.,Oncology Hospital |
Neri N.,Oncology Hospital
Medical Oncology | Year: 2013
Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised. © 2013 Springer Science+Business Media New York.
Castro-Manrreza M.E.,Oncology Hospital |
Montesinos J.J.,Oncology Hospital
Journal of Immunology Research | Year: 2015
Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiation into mesenchymal lineages and that can be isolated from various tissues and easily cultivated in vitro. Currently, MSCs are of considerable interest because of the biological characteristics that confer high potential applicability in the clinical treatment of many diseases. Specifically, because of their high immunoregulatory capacity, MSCs are used as tools in cellular therapies for clinical protocols involving immune system alterations. In this review, we discuss the current knowledge about the capacity of MSCs for the immunoregulation of immunocompetent cells and emphasize the effects of MSCs on T cells, principal effectors of the immune response, and the immunosuppressive effects mediated by the secretion of soluble factors and membrane molecules. We also describe the mechanisms of MSC immunoregulatory modulation and the participation of MSCs as immune response regulators in several autoimmune diseases, and we emphasize the clinical application in graft versus host disease (GVHD). © 2015 Marta E. Castro-Manrreza and Juan J. Montesinos.
Mayani H.,Oncology Hospital
Archives of Medical Research | Year: 2011
During the last 23 years, cord blood research has played important roles both in experimental and clinical hematology. Cord blood-derived hematopoietic stem and progenitor cells have been shown to possess particular biological features and their study has been very important in our understanding of hematopoietic development. Today, >20,000 umbilical cord blood (UCB) transplants have been performed worldwide and ∼460,000 UCB units are being stored in >47 UCB banks worldwide. Here a brief overview on some of the most relevant issues regarding cord blood research is presented. © 2011 IMSS.
Aslan S.,Oncology Hospital
Bratislavské lekárske listy | Year: 2011
Wound infection, flap necrosis rates and peripheral complete blood cell count changes related to intraoperative whole-blood transfusions were investigated. Evidence is growing that whole-blood cell transfusions are immunosuppressive and predispose patients to postoperative infections. 102 female breast carcinoma patients with hemoglobin levels = 10 g/dl before modified radical mastectomy and < 10 g/dl intraoperatively but with no signs of oxygen debt were included. Group I included patients who had received two units of whole-blood transfusions intraoperatively. Patients who had received no transfusion were in group II. Peripheral complete blood cell count, wound infection rates and flap necrosis were compared. Perioperative neutrophile and monocyte count increased in both groups. This increase was especially significant in the transfused group (p < 0.05). In both groups, these changes returned to normal levels on the tenth postoperative day. The decreased perioperative basophile count did not return to the baseline even on the tenth postoperative day in group I (p < 0.05). Lymphocyte count, and flap necrosis did not differ between the groups (p > 0.05). Wound infection seemed to take place and increase in the transfused group (p < 0.05). Two units of whole-blood transfusions seem to increase wound infection and decrease basophile count in this series (Tab. 3, Ref. 30).
Purizaca J.,Oncology Hospital |
Purizaca J.,CINVESTAV |
Meza I.,CINVESTAV |
Pelayo R.,Oncology Hospital
Archives of Medical Research | Year: 2012
B-cell acute lymphoblastic leukemia (B-ALL) is a hematological disorder characterized by malignant and uncontrolled proliferation of B-lymphoid precursor cells in bone marrow. Over the last few years remarkable advances have been made in identifying genetic aberrations, patterns of abnormal transcriptional activity controlling early fate decisions and environmental cues that may influence leukemic development. In this review we focus on the structure of the early lymphoid system and the current knowledge about cell composition and function of the hematopoietic microenvironment that might control progenitor cell activity and lead to differentiation, proliferation and survival of developing B leukemic precursors. Learning the biology of special leukemic niches is central to understanding the pathogenesis of B-ALL and for the development of novel therapies. © 2012 IMSS.