• Peak C-peptide following Mixed Meal Tolerance Test
  

• Insulin Dose
  
• Autoantibody Levels
  
• T-cell functional response assays
  
• Cytokine levels
  

Objective:

Our goal is to transfuse autologous umbilical cord blood into 23 children with T1D in an attempt to re-establish immune tolerance and perhaps regenerate pancreatic islet insulin-producing beta cells and improve blood glucose control. As secondary goals, we aim to study the potential changes in metabolism/immune function leading to islet regeneration.

Background/Rationale:

Stem cells provide an exciting approach towards curing T1D. Autologous bone marrow transplants have been used successfully for patients undergoing high dose chemotherapy, and for a variety of cancers and autoimmune disorders such as multiple sclerosis, lupus, and rheumatic disorders. Recent studies in immunodeficient mice with chemically-induced pancreatic damage have shown that bone marrow-derived stem cells preferentially home to the pancreas and may have the capacity to initiate pancreatic regeneration, thereby restoring the endothelial interactions in the pancreas and correcting the associated elevated blood sugar levels Human umbilical cord blood cells transfused into a model of amyotrophic lateral sclerosis (ALS) resulted in delayed disease progression of two to three weeks and increased lifespan. Umbilical cord blood has shown promise as an excellent source for deriving stem cell populations, and has been used successfully in transplantation for a variety of diseases, including acute lymphocytic and myeloid leukemia, lymphoma, Fanconi anemia, and sickle cell disease. Furthermore, umbilical cord blood-derived stem cells have the capacity to differentiate into a variety of non-blood cell types, including hepatocytes, neural cells, and endothelial cells. In addition, umbilical cord blood contains a greater proportion of hematopoietic stem cells than bone marrow.

In addition, cord blood contains a large number of immune cells called regulatory T cells, These regulatory T cells may be helpful in diminishing autoimmunity. The need to re-establish tolerance in patients with established autoimmunity provides another potential mechanism for cord blood as a therapy for type 1 diabetes.

Description of Project:

23 children > 1 year of age with T1D and stored umbilical cord blood are being be recruited. The cord blood will be infused into the children in the GCRC in an attempt to regenerate pancreatic islet insulin-producing beta cells and improve blood glucose control. As secondary goals, we aim to track the migration of transfused cord blood stem and study the potential changes in metabolism/immune function leading to islet regeneration.

Anticipated Outcome:

It is hoped that there will be preservation of beta cell function assessed by mixed meal stimulated C-peptide secretion. Changes in immunological markers/function may be observed

Relevance to Type I Diabetes:

Type 1 diabetes is still associated with tremendous morbidity and premature mortality. Patients require multiple daily insulin injections throughout their lives as well as close monitoring of their diet and blood sugar levels to prevent complications. Unfortunately, there is presently no permanent cure for diabetes. Whole pancreas or islet cell transplantation is available only to a very limited number of patients and necessitates potential lifelong immunosuppressive therapy. The need to find a cure for T1D cannot be overstated -autologous stem cell transfusions either with their potential to differentiate into islet cells or provide immune tolerance that leads to islet regeneration appear to be a safe and potentially viable option.

Inclusion Criteria:

1. Must have a diagnosis of T1D and have stored umbilical cord blood in an AABB and/or FACT accredited cord bank.
2. TID diagnosis will be defined as having a clear history of polydipsia, polyphagia, polyuria, and weight loss consistent with a clinical diagnosis, diagnosis will mot be based solely upon the presence of autoantibodies.
3. Cord blood meets all selection and testing criteria (see below).
4. Able to complete mixed meal tolerance / glucagon stimulation test.
5. Normal screening values for CBC, Renal function and electrolytes (BMP).
6. Willing to comply with intensive diabetes management

Exclusion Criteria:

1. Complicating medical issues that would interfere with blood drawing or monitoring.
2. Chronic use of steroids or other immunosuppressive agents for other conditions.
3. Positive infectious disease markers from mothers' blood or cord at time of collection (See below for details).
4. Any evidence of illness on planned infusion date (i.e. fever >38.5 C, vomiting, diarrhea, wheezing, or crackles).