[ Diabetes Type 2 ]

Autologous Umbilical Cord Blood Transfusion in Very Young Children With Type 1 Diabetes

The researchers hope the blood, rich in stem cells and immune cells, will help reboot the immune systems of children at risk of the condition, which happens when the body attacks and kills its own insulin-producing cells. Maria Craig, professor of paediatric endocrinology, the University of Sydney and Sydney Children’s Hospital Network, recently joined us on Share the Science to discuss the CoRD study (Cord blood Reinfusion in Diabetes). In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Functional evaluation, vascular and white-matter changes, neuroinflammation, and miR-126 effects were measured in vivo and in vitro. hUCB-MSC effectively prevented diabetic renal injury except renal and glomerular hypertrophy without a significant effect on blood glucose. We assessed cord-blood levels of leptin and insulin in 56 neonates born to diabetic mothers (preexisting diabetes n = 15, gestational diabetes mellitus [GDM] n = 41) and in 25 born to control subjects and investigated whether leptin levels are related to ponderal index (PI), sex, pre-eclampsia, or fetal insulinemia. But Professor Craig said the evidence of the value of T-cells in conditions such as type 1 diabetes, heart disease, stroke and neurological disorders had only increased since the study was launched in 2012..

An autologous cord blood infusion does not change the natural course of metabolic and immune parameters after disease onset. Additionally, pH, pCO2, pO2 and base excess were measured in both vessels and compared to identify and exclude double venous samples. However, these cell clusters with blue cytoplasm were present in sections from GIII indicating the presence of injected differentiated UCBMSCs (Photomicrograph 1). Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood–based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes. Autologous UCB infusion followed by daily supplementation with vitamin D and DHA was safe but failed to preserve C-peptide. In terms of modern medicine type 1 diabetes is considered an autoimmune disease in which the insulin-producing cells in the pancreas are destroyed by autoantibodies. Although several agents have shown and continue to show promise, no single agent has succeeded in demonstrating long-term success in preventing or reversing type 1 diabetes as a means of standard medical practice.

More recently, efforts have focused on the use of either autologous or allogeneic hematopoietic stem/progenitor cells as potential immunoregulatory agents to reverse this disease. Whereas hematopoietic stem cells have successfully been directed in vitro to differentiate into insulin- and C-peptide–producing cells (5), and infusion of human hematopoietic stem cells into diabetic animals has demonstrated reversal of disease (6,7), the potential of such cells to provide a source of safe and effective immunomodulation may be of the greatest importance in treating type 1 diabetes, but this has yet to be realized (8–10). The New Heroin Epidemic From prescription drugs to illegal narcotics, the DEA reports an alarming surge in drug use and abuse among Americans over recent years. Umbilical cord blood contains a robust population of immature unprimed highly functional regulatory T-cells (Tregs) (15). These highly functional Tregs could, in theory, limit inflammatory cytokine responses and anergize effector T-cells, which are thought to play a key role in cellular-mediated autoimmune processes (16,17). As such, umbilical cord blood Tregs have become a major focus of our work in designing cell-based therapies for children with type 1 diabetes (18). Practical matters provide an additional rationale for umbilical cord blood–based therapies.

First, the lack of low-risk (i.e., safe) diabetes intervention trials seeking to reverse disease, especially for young children with type 1 diabetes, renders the potential use of umbilical cord blood particularly appealing. Second, as the rates of umbilical cord blood storage continue to increase exponentially, the number of potential subjects for autologous umbilical cord blood–based clinical trials continues to grow. Schatz, MD, Professor and Associate Chairman of Pediatrics at the University of Florida College of Medicine and senior author of the study, posited three potential mechanisms for the results in a recent interview. Finally, as umbilical cord blood storage facilities continue to reevaluate storage methods that would allow for multiple withdrawals, potential exists for protocols that involve cell expansion and/or multiple cell infusions. Although we focused our interest on the notion that umbilical cord blood Tregs might affect tolerance, we also considered that autologous umbilical cord blood transfusion in the setting of type 1 diabetes may help mitigate the autoimmune process by a variety of mechanisms beyond those of direct immune modulation (19). First, umbilical cord blood stem cells may migrate to the damaged pancreas, where they could differentiate into insulin-producing β-cells (2). In addition, umbilical cord blood stem cells might act as nurse cells to foster the proliferation or replication of new β-cells from remnant viable tissue (20).

Potency: these stem cells are younger; grow faster and for longer than stem cells from other adult stem cell sources. Based on available preclinical data and the agreement that infusion of minimally manipulated autologous umbilical cord blood was likely to be extremely safe, we performed an unblinded observational pilot study to determine whether autologous umbilical cord blood infusion could impede the type 1 diabetes autoimmune process and preserve remaining endogenous insulin production. Peak C-peptide after a standard mixed-meal tolerance test (MMTT), A1C, and daily insulin requirement were set as the primary outcome variables, with a variety of immunologic markers assessed for their potential mechanistic insights. A detailed description of the study protocol’s design, without results, has been published previously (18). Choosing to bank the cord blood and tissue from all pregnancies is highly encouraged. 1. Briefly, subjects aged >1 year with type 1 diabetes (established by clinical presentation and presence of type 1 diabetes–associated autoantibodies) and for whom autologous umbilical cord blood had been stored in an American Association of Blood Banks (AABB)- or Foundation for the Accreditation for Cellular Therapy (FACT)-recognized cord blood bank, were recruited for participation in this single-center study (NCT00305344; FDA IND BB-11918).

This Federal Drug Administration (FDA)-approved study of 23 subjects completed enrolment in November 2008. Circumstances and timing of ear, skin and body piercings are evaluated by the cord blood bank. For this report, the first 15 of these 23 subjects who completed at least 1 year postinfusion follow-up are reported herein. Group B patients, who went in with no insulin activity whatsoever, were already progressing to normal insulin activity within 12 weeks and nearly matching normal levels at the end of the study (40 weeks). Autologous cord blood infusion in type 1 diabetes: study timeline. Our study was designed as a 2-year observational study of the effects of autologous cord blood infusion in children with type 1 diabetes. Each child was followed every 3 months during the first year postinfusion and every 6 months during the second year postinfusion.

Blood was obtained for metabolic and immunologic studies at each visit. Mean time from type 1 diabetes diagnosis to umbilical cord blood infusion was 6 months. Herein, we report 1 year postinfusion data on the first 15 umbilical cord blood recipients to reach 1 year of post–cord blood infusion follow-up. T1D, type 1 diabetes; UCB, umbilical cord blood; q, every. Parents own the cord blood until the baby turns 18. Thereafter, the subject’s remaining umbilical cord blood unit was shipped to the University of Florida and stored until transfused. Subjects were then scheduled to perform a standard 2-h MMTT to determine baseline endogenous insulin production and A1C values.

Additional blood was drawn for routine clinical assessments as well as metabolic and immunologic analyses.

Tags: , ,