Diabetes Complications, Diabetic Retinopathy
Conditions
Keywords
inducible pluripotent stem cells
Brief summary
This study proposes to carefully examine the hypothesis that human inducible pluripotent stem cells (iPSCs) can be effectively employed as a future therapeutic option for individuals with diabetic retinopathy and macular ischemia. iPSCs will be generated from the peripheral blood cells of subjects with diabetes and age matched controls. The human iPSC cells will be used to generate mesoderm cells for injection into the vitreous cavity of diabetic rodents and primate eyes. The ability of mesoderm cells to generate endothelial cells and pericytes in areas of degenerated capillaries will be examined. The human iPSCs will also be used to generate hematopoietic CD34+CD45+ cells. The combination of CD34+CD45+ cells derived from iPSCs and iPSC derived mesoderm will be examined in combination for their potentially beneficial effect to enhance the vessel formation.
Detailed description
Vascular complications due to diabetes mellitus (DM) are the result of sustained vascular injury with insufficient vascular repair. In chronic diabetes, vascular reparative mechanism can be lost resulting in development of microvascular complications (MVC), such as diabetic retinopathy (DR). We assessed the reparative function of progenitor cells that circulate in the peripheral blood of diabetic individuals and found that the vascular wall-derived progenitor cells, endothelial colony forming cells (ECFCs), were depleted in diabetics with MVC. Bone marrow-derived progenitor cells, CD45+CD34+ were dysfunctional in diabetics with MVC. We found that human inducible pluripotent stem cells (hiPSCs)-derived ECFCs displayed the ability to form functional and durable blood vessels in vivo and conferred therapeutic revascularization by connecting with and remaining integrated with host rodent vessels long term. We characterized a mesoderm subset (SSEA5-KNA+ cells) generated from hiPSCs that gives rise to ECFCs. Finally, we used hiPSCs to generate CD34+CD45+ cells and tested the impact of co-administration of these cells with ECFCs within the vitreous. The addition of CD34+CD45+ cells with ECFCs resulted in the enhanced survival, function and reparative ability of the ECFCs. This beneficial effect was mediated by reducing retinal oxidative stress and inflammation. These novel and paradigm shifting findings led us to hypothesize: the hiPSC-derived-mesoderm subset (SSEA5-KNA+) can be utilized for long term revascularization of vasodegenerative capillaries and their reparative action can be further enhanced by coinjection of CD34+CD45+ cells that provide anti-oxidant and anti-inflammatory effects.
Interventions
BIOLOGICALGeneration of inducible pluripotent stem cells
Generation of inducible pluripotent stem cells from peripheral blood cells.
Sponsors
University of Alabama at Birmingham
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
21 Years to 98 Years
Healthy volunteers
Yes
Inclusion criteria
* Any man or woman between the ages of 21- 98 years of age will be eligible to participate. To participate in the study as a study subject we will require: a) the subject must either carry the diagnosis of diabetes or be a healthy aged control and b) the patient be willing and have the ability to cooperate with the eye exam and skin punch biopsy protocol.
Exclusion criteria
* We will apply the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Generating iPSCs from peripheral blood | From blood draw to 4 months | Blood will be collected from the patient and cells will be isolated and shipped to ALSTEM for generation of iPSCs |
| Differentiate iPSCs into CD34+ cells and mesoderm | 4 months to 4 years | Specific cell culture conditions will be used to differentiate the cells into these two distinct populations |
Countries
United States
Contacts
CONTACTJennifer Moorer
PRINCIPAL_INVESTIGATORMaria B Grant, MD
1954
Outcome results
None listed