Autologous Adult Stem Cells to Patients With Type 1 Diabetes and a Successful Renal Transplant
Condition: Type 1 Diabetes; Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a phase I study to assess the safety and tolerability of infusing expanded stem cells
      into the pancreas of patients with type I diabetes and a successful renal transplant. The
      stem cells used in this study occur naturally in the body and are collected from each
      recipient by a procedure called leukapheresis. The cells are then expanded and differentiated
      into insulin-like cells in a sterile suite before being injected into the body or tail of the
      pancreas of the recipient.
    

Detailed description: 
      Islet transplantation as a potential treatment for diabetes has been investigated extensively
      over the past 10 years. Such an approach, however, will always be limited mainly because it
      is difficult to obtain sufficiently large numbers of purified islets from cadaveric donors.
      One alternative to organ or tissue transplantation is to use a renewable source of cells.
      Adult stem cells are clonogenic cells capable of both self-renewal and multilineage
      differentiation. These cells have the potential to proliferate and differentiate into any
      type of cell and to be genetically modified in vitro, thus providing cells, which can be
      isolated and used for transplantation.

      Recent studies have given well-defined differentiation protocols, which can be used to guide
      stem cells into specific cell lineages as neurons, cardiomyocytes and insulin-secreting
      cells. Moreover, these derived cells have been useful in different animal models. In this
      regard, insulin-secreting cells derived from R1 mouse embryonic stem cells restore blood
      glucose concentrations to normal when they are transplanted into streptozotocin-induced
      diabetic animals. Our group has isolated stem cells (Cluster Designated (CD) 34 positive
      subset of stem cells) that are capable of differentiating into multiple tissue types ex vivo.
      In defined conditions, in culture, about 40 percent of the cells produce insulin and reduce
      blood sugar levels in streptozotocin-induced mice.

      Clinically, we have performed a phase I trial of stem cell administration to patients with
      liver insufficiency. The procedure was well tolerated with no specific side effects and with
      sustained signs of clinical benefit. These results support this protocol for the application
      of adult stem cell therapy in the treatment of diabetes.

      In order to evaluate potential clinical applications for these recent advances we have
      designed a prospective Phase I clinical study of the expanded progeny of an adult CD34
      positive subset (InsulinCytes) injected directly into the body and tail of the pancreas of
      the participants via selective catheterisation of the splenic artery. The study group
      consists of patients with complicated diabetes mellitus type I plus kidney transplantation
      with the aim of ascertaining whether this confers clinical benefit as a treatment model for
      diabetes.

      Granulocyte colony-stimulating factor (G-CSF) will be administered to suitable patients to
      mobilise their haematopoietic stem cells (HSCs) from the bone marrow into the peripheral
      circulation. These blood cells will be collected from each patient by leukapheresis. CD34
      positive stem cells will then be isolated by immunoselection and introduced into a Nunc cell
      factory where the subset of CD34 positive stem cells will be allowed to attach to the plastic
      trays within the cell factory for 2 hours at 37 degrees C in 5 percent carbon dioxide. After
      this period the non-attached CD34 positive cells will be washed from the system and the
      progeny of the attached cells secreted into the supernatant media expanded in the presence of
      growth medium supplemented with growth factors. At the end of 6 days expansion, the stem
      cells will be differentiated into insulin and c-peptide protein excreting cells over the next
      14 days by the addition of specified reagents/growth factors and continued incubation at 37
      degrees C in 5 percent carbon dioxide in accordance with the principles of Good Manufacturing
      Practice (GMP). As an optional step the cells can be labelled with iron oxide to allow
      tracking of the cells by Magnetic Resonance Imaging (MRI) scan, before being infused into the
      patient.

      An ongoing institute experience with liver failure patients who have been infused with
      undifferentiated stem cells has shown that an administered dose of up to 2 x 10 log 9 cells
      was well tolerated. The proposed study group will consist of 10 Type I or Type 2 diabetic
      patients who have had a successful previous kidney transplant.

      The primary purpose of the study is to assess the safety and tolerance of stem cell infusion
      into the pancreas and then to assess the impact of this new modality in the treatment of
      diabetes.
    

Intervention name(s): Autologous CD34+ stem cells
Intervention type(s): Biological
Intervention description(s): Up to 5 x 10 log 8 of autologous stem cells on a single occasion
Intervention model: Single Group Assignment
Intervention model description: Autologous stem cells
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: diabetes type I; diabetes type 2; renal transplant; stem cells; successful renal transplant