Enforced fucosylation of cord blood hematopoietic cells accelerates neutrophil and platelet engraftment after transplantation.
نویسندگان
چکیده
Delayed engraftment is a major limitation of cord blood transplantation (CBT), due in part to a defect in the cord blood (CB) cells' ability to home to the bone marrow. Because this defect appears related to low levels of fucosylation of cell surface molecules that are responsible for binding to P- and E-selectins constitutively expressed by the marrow microvasculature, and thus for marrow homing, we conducted a first-in-humans clinical trial to correct this deficiency. Patients with high-risk hematologic malignancies received myeloablative therapy followed by transplantation with 2 CB units, one of which was treated ex vivo for 30 minutes with the enzyme fucosyltransferase-VI and guanosine diphosphate fucose to enhance the interaction of CD34(+) stem and early progenitor cells with microvessels. The results of enforced fucosylation for 22 patients enrolled in the trial were then compared with those for 31 historical controls who had undergone double unmanipulated CBT. The median time to neutrophil engraftment was 17 days (range, 12-34 days) compared with 26 days (range, 11-48 days) for controls (P = .0023). Platelet engraftment was also improved: median was 35 days (range, 18-100 days) compared with 45 days (range, 27-120 days) for controls (P = .0520). These findings support ex vivo fucosylation of multipotent CD34(+) CB cells as a clinically feasible means to improve engraftment efficiency in the double CBT setting. The trial is registered to www.clinicaltrials.gov as #NCT01471067.
منابع مشابه
Association between CRP Level on Admission Day and Length of Hospitalization and Engraftment in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Background and purpose: Several studies investigated the role of C-reactive protein (CRP) during transplantation and inflammation, and clinical outcomes after stem cell transplantation. In this study, we examined the relationship between the earliest CRP level on admission day, and the first outcome after transplantation, myeloid and platelet engraftment, and the length of hospitalization in p...
متن کاملRelation between Age, Gender, Number of Blood Products Received and Diagnosis with Engraftment and Length of Hospital Stay in Patients Undergoing Autologous Stem Cell Transplantation
Background and purpose: Autologous hematopoietic stem cell transplantation may be one of the best treatment options for some patients with hematological malignancies. The process of stem cell homing in the bone marrow and the production and proliferation of denovo cell populations is called engraftment and could be considered as one of the key factors in the success of stem cell transplantation...
متن کاملEx vivo fucosylation improves human cord blood engraftment in NOD-SCID IL-2Rγ(null) mice.
Delayed engraftment remains a major hurdle after cord blood (CB) transplantation. It may be due, at least in part, to low fucosylation of cell surface molecules important for homing to the bone marrow microenvironment. Because fucosylation of specific cell surface ligands is required before effective interaction with selectins expressed by the bone marrow microvasculature can occur, a simple 30...
متن کاملتاثیر آشیانههای جفتی شبیهسازی شده با داربست پلی لاکتیک اسید در تکثیر سلولهای بنیادی خونساز مشتق از بافت جفت انسانی
Background and Objective: Nowadays, although umbilical cord blood is a commonly used source of hematopoietic stem cell, its low frequency of these cells is the main factor limiting its clinical application. The transplantation of hematopoietic stem cells derived from placenta tissue along with umbilical cord blood cells of the same sample may be an appropriate approach to solve this problem. In...
متن کاملCord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation.
Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Blood
دوره 125 19 شماره
صفحات -
تاریخ انتشار 2015