Publications by authors named "Ian K McNiece"

The in vivo depletion of recipient and donor T lymphocytes using antithymocyte globulin (ATG; Thymoglobulin) is widely adopted in allogeneic hematopoietic stem cell transplantation (HCT) to reduce the incidence of both graft failure and graft-versus-host disease (GVHD). However, excess toxicity to donor lymphocytes may hamper immune reconstitution, compromising antitumor effects and increasing infection. Granulocyte-colony stimulating factor (G-CSF) administered early after HCT may increase ATG-mediated lymphotoxicity.

View Article and Find Full Text PDF

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018.

View Article and Find Full Text PDF

Cell and gene therapy is a promising and disruptive new field of medicine for diseases lacking effective treatments. Collaboration among stakeholders has become critically important as investigators, health care providers, manufacturers, couriers, data registries, regulators and payers all become more invested in the success of this field. Many organizations have collaborated with each other to increase clarity, advocate for improvements and share lessons learned.

View Article and Find Full Text PDF

In the absence of prospective studies that examine the effect of conditioning regimen intensity after T-cell-replete haploidentical transplant for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS), a retrospective cohort analysis was performed. Of the 1325 eligible patients (AML, n = 818; ALL, n = 286; and MDS, n = 221), 526 patients received a myeloablative regimen and 799 received a reduced-intensity regimen. Graft-versus-host disease prophylaxis was uniform with posttransplant cyclophosphamide, a calcineurin inhibitor, and mycophenolate mofetil.

View Article and Find Full Text PDF

Aim: Endothelial cells (ECs), isolated from peripheral blood (PB), bone marrow (BM) and cord blood (CB), are limited in numbers and expansion has had limited success. We used a novel serum-free medium (EndoGo) to evaluate effects on expansion of CB-derived ECs.

Materials & Methods: Flow cytometry and matrigel were used to determine expansion of ECs and for determination of the EC progenitor cell.

View Article and Find Full Text PDF

We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant.

View Article and Find Full Text PDF

Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field.

View Article and Find Full Text PDF

Regenerative medicine offers new hope for many debilitating diseases that result in damage to tissues and organs. The concept is straightforward with replacement of damaged cells with new functional cells. However, most tissues and organs are complex structures involving multiple cell types, supportive structures, a microenvironment producing cytokines and growth factors and a vascular system to supply oxygen and other nutrients.

View Article and Find Full Text PDF

Allogeneic hematopoietic stem cell transplantation is an important treatment option for fit patients with poor-risk hematological malignancies; nevertheless, the lack of available fully matched donors limits the extent of its use. Umbilical cord blood has emerged as an effective alternate source of hematopoietic stem cell support. Transplantation with cord blood allows for faster availability of frozen sample and avoids invasive procedures for donors.

View Article and Find Full Text PDF

Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown.

Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments.

Methods And Results: Biplane ventriculographic and endocardial tracings were recorded.

View Article and Find Full Text PDF

Importance: Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial.

Objective: To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy.

Design, Setting, And Patients: A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013).

View Article and Find Full Text PDF

Background Aims: Advantages associated with the use of cord blood (CB) transplantation include the availability of cryopreserved units, ethnic diversity and lower incidence of graft-versus-host disease compared with bone marrow or mobilized peripheral blood. However, poor engraftment remains a major obstacle. We and others have found that ex vivo fucosylation can enhance engraftment in murine models, and now ex vivo treatment of CB with fucosyltransferase (FT) VI before transplantation is under clinical evaluation (NCT01471067).

View Article and Find Full Text PDF

Recent studies suggest that bone marrow (BM)-derived stem cells have therapeutic efficacy in neonatal hyperoxia-induced lung injury (HILI). c-kit, a tyrosine kinase receptor that regulates angiogenesis, is expressed on several populations of BM-derived cells. Preterm infants exposed to hyperoxia have decreased lung angiogenesis.

View Article and Find Full Text PDF

Context: Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared.

Objective: To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM.

View Article and Find Full Text PDF

During mouse embryogenesis, hematopoietic development takes place in several distinct anatomic locations. The microenvironment of different hematopoietic organs plays an important role in the proliferation and maturation of the hematopoietic cells. We hypothesized that fetal stromal cells would be distinct to adult bone marrow (BM)-derived stromal cells because the BM contributes mainly to the homeostasis of hematopoietic stem cells (HSCs), while extensive expansion of HSCs occurs during fetal development.

View Article and Find Full Text PDF

Stem cell therapy for repair of damaged cardiac tissue is an attractive option to improve the health of the growing number of heart failure patients. Mesenchymal stem cells (MSCs) possess unique properties that may make them a better option for cardiac repair than other cell types. Unlike other adult stem cells, they appear to escape allorecognition by the immune system and they have immune-modulating properties, thus making it possible to consider them for use as an allogeneic cell therapy product.

View Article and Find Full Text PDF

Human mesenchymal stem cells (MSCs) are multipotential and are detected in bone marrow (BM), adipose tissue, placenta, and umbilical cord blood (UCB). In this study, we examined the ability of UCB-derived MSCs (UCB-MSCs) to support ex vivo expansion of hematopoietic stem/progenitor cells (HSPCs) from UCB and the engraftment of expanded HSPCs in NOD/SCID mice. The result showed that UCB-MSCs supported the proliferation and differentiation of CD34+ cells in vitro.

View Article and Find Full Text PDF

Background: Herein are reported the results obtained in all multiple myeloma patients transplanted with peripheral blood hematopoietic progenitor cells submitted to ex vivo expansion.

Study Design And Methods: Patients had blood progenitor cell mobilization with cyclophosphamide and filgrastim. CD34+ cells were expanded for 10 days in a medium containing granulocyte-colony-stimulating factor (G-CSF), stem cell factor, and megakaryocyte growth and development factor (MGDF).

View Article and Find Full Text PDF

A novel indirect co-culture system was established to support ex vivo expansion of hematopoietic progenitors in umbilical cord blood (UCB) by using thrombopoietin (TPO)/Flt-3 ligand (FL)-transduced human-marrow-derived mesenchymal stem cells (tfhMSCs) as a feeder. UCB CD34+ cells were isolated and cultured by using five culture systems in serum-containing or serum-free medium. Suitable aliquots of cultured cells were taken to monitor cell production, clonogenic activity, and long-term culture-initiating culture (LTC-IC) output.

View Article and Find Full Text PDF

Objective: To explore the biological characteristics of mesenchymal stem cells (MSC) derived from umbilical cord blood (UCB) and their supporting capacities in ex vivo expansion of hematopoietic stem/progenitor cells (HSPCs).

Methods: Low-density mononuclear cells (MNCs) from UCB were cultured in IMDM containing 20% FBS to form confluent adherent cells through 15 passages. Some cytokines in the conditioned medium were determined with ELISA.

View Article and Find Full Text PDF

Purpose: The purpose of this study was to evaluate the prognostic effect of early posttransplant lymphocyte recovery in patients with advanced breast cancer receiving high-dose chemotherapy with autologous hematopoietic progenitor cell transplantation.

Experimental Design: We analyzed the effect of the absolute lymphocyte count on day +15 posttransplant on freedom from relapse and overall survival in patients with high-risk primary breast cancer or metastatic breast cancer, enrolled between 1990 and 2001 in prospective high-dose chemotherapy trials, using a uniform regimen of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea.

Results: Four hundred and seventy-six patients (264 high-risk primary breast cancer and 212 metastatic breast cancer patients) were evaluated at median follow-up of 8 years (range, 1.

View Article and Find Full Text PDF

Background And Objectives: Human mesenchymal stem/progenitor cells (MSPC) ar pluripotent, being the precursors for marrow stroma, bone, cartilage, muscle and connective tissues. Although the presence of hematopoietic stem/progenitor cells (HSPC) in umbilical cord blood (UCB) is well known, that of MSPC has been not fully evaluated.

Design And Methods: In this study, we examined the immunophenotype, the supporting function in relation to ex vivo expansion of hematopoietic stem progenitor cells and the chondrogenic differentiation of cultured cells with characteristics of MSPC from UCB.

View Article and Find Full Text PDF

Objective: To explore the rapid neutrophil engraftment and long-term hematopoietic reconstitution.

Methods: Mononuclear cells (MNCs) were isolated from 5-Fu treated male BDF1 mouse bone marrow and CD(34)(+)/c-kit(+) cells were selected from the MNCs by using MoFlo Cell Sorter. MNCs and CD(34)(+)/c-kit(+) cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) in a two-step expansion.

View Article and Find Full Text PDF

To examine the effects of co-culture with bone marrow mesenchymal stem cells on expansion of hematopoietic stem/progenitor cells and the capacities of rapid neutrophil engraftment and hematopoietic reconstitution of the expanded cells, we expanded mononuclear cells (MNCs) and CD34+/c-kit+ cells from mouse bone marrow and transplanted the expanded cells into the irradiated mice. MNCs were isolated from mouse bone marrow and CD34+/c-kit+ cells were selected from MNCs by using MoFlo Cell Sorter. MNCs and CD34+/c-kit+ cells were co-cultured with mouse bone marrow-derived mesenchymal stem cells (MSCs) under a two-step expansion.

View Article and Find Full Text PDF

Information is rapidly emerging regarding the important role of the arterial vasa vasorum in a variety of systemic vascular diseases. In addition, increasing evidence suggests that progenitor cells of bone marrow (BM) origin may contribute to postnatal neovascularization and/or vascular wall thickening that is characteristic in some forms of systemic vascular disease. Little is known regarding postnatal vasa formation and the role of BM-derived progenitor cells in the setting of pulmonary hypertension (PH).

View Article and Find Full Text PDF