Human iPSC for Repair of Vasodegenerative Vessels in Diabetic Retinopathy

NCT ID: NCT03403699

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-01-11
• Study Completion Date: 2027-12-31

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.

Conditions

Diabetes Complications; Diabetic Retinopathy

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

nondiabetics

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 be a healthy control and b) the subject be willing and have the ability to cooperate with the eye exam and blood draw.

Generation of inducible pluripotent stem cells

Intervention Type: BIOLOGICAL

Generation of inducible pluripotent stem cells from peripheral blood cells.

Diabetic

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) carry the diagnosis of diabetes and b) the subject be willing and have the ability to cooperate with the eye exam and blood draw.

Generation of inducible pluripotent stem cells

Intervention Type: BIOLOGICAL

Generation of inducible pluripotent stem cells from peripheral blood cells.

Interventions

Generation of inducible pluripotent stem cells

Generation of inducible pluripotent stem cells from peripheral blood cells.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 98 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Maria Grant

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Maria B Grant, MD

Role: PRINCIPAL_INVESTIGATOR

1954

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jennifer Moorer

Role: CONTACT

jmoorer@uabmc.edu

205 325 8674

Facility Contacts

Jennifer Moorer

Role: primary

jmoorer@uabmc.edu

2053258674

Other Identifiers

300000173

Identifier Type: -

Identifier Source: org_study_id