Human IPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy

Last updated: October 4, 2024
Sponsor: University of Alabama at Birmingham
Overall Status: Active - Recruiting

Phase

N/A

Condition

Retina

Diabetic Retinopathy

Treatment

Generation of inducible pluripotent stem cells

Clinical Study ID

NCT03403699
300000173
  • Ages 21-98
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Any man or woman between the ages of 21- 98 years of age will be eligible toparticipate. To participate in the study as a study subject we will require: a) thesubject must either carry the diagnosis of diabetes or be a healthy aged control andb) the patient be willing and have the ability to cooperate with the eye exam andskin punch biopsy protocol.

Exclusion

Exclusion Criteria:

  • We will apply the following exclusion criteria: a) evidence of ongoing acute orchronic infection (HIV, Hepatitis B or C, tuberculosis); b) ongoing malignancy; c)cerebral vascular accident or cerebral vascular procedure; d) current pregnancy; e)history of organ transplantation; f) presence of a graft (to avoid any effect of thegraft on inflammatory parameters; and g) patients with anemia. Subjects with AMD,glaucoma, uveitis, known hereditary degenerations or other significant ocularcomplications other than diabetic retinopathy will be excluded.

Study Design

Total Participants: 20
Treatment Group(s): 1
Primary Treatment: Generation of inducible pluripotent stem cells
Phase:
Study Start date:
January 11, 2018
Estimated Completion Date:
January 31, 2026

Study 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.

Connect with a study center

  • University of Alabama at Birmingham

    Birmingham, Alabama 35294
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.