# Diabetic skin influences on outgrowth of human iPSC-derived sensory axons

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $450,313

## Abstract

Project Summary:
This proposal details a new research plan to examine the differential effects of neuronal origin
and axonal target environment on nerves from people with diabetes mellitus 2 (DM2) to
understand why these nerves degenerate and have reduced plasticity compared to their heathy
counterparts, especially within the epidermis. Axon growth of sensory neurons derived from
human induced pluripotent stem cells (iPSCs) will be studied in the presence of skin biopsied
from control subjects and patients with diabetes and varying degrees of peripheral neuropathy.
We hypothesize:
 1) That cellular origin matters and that sensory axons derived from iPSCs of
 subjects with DM2 and peripheral neuropathy will grow and regenerate more
 slowly than sensory neurons derived from healthy control iPSCs.
 2) That the regenerative environment also plays an important role, perhaps more
 important than neuronal origin: that sensory axons, irrespective of their origin,
 will regenerate more slowly on a matrix of skin from subjects with DM2 and
 peripheral neuropathy compared to a matrix of skin from healthy control
subjects.
 Understanding the role of these different potential influences on human axonal
regeneration will place us in a better position in the future to identify the molecules involved and
therapeutic targets for diabetic neuropathy- a condition that has defied meaningful clinical
advances beyond optimizing glucose control.
 Sensory neurons derived from human iPSCs hold promise for advancing the field of
small fiber neuropathy in general, including diabetic peripheral neuropathy (DPN). However,
interactions of iPSC-derived sensory neurons with the epidermis have not been explored.
Therefore, it is important to perform novel experiments, such as those proposed here, that
specifically examine axons of iPSC-derived sensory neurons to determine potential factors that
influence their degeneration when they are in milieu, over biopsied skin that mimics human
conditions.
 We are addressing this knowledge gap by utilizing microfluidic chambers that separate
axons from neuronal cell bodies in order to study the basic pathobiology of the distal sensory
axons of diabetic patients. Through this proposal, we anticipate the development of a system
derived from human cells to interrogate factors that inhibit axonal plasticity in DPN.

## Key facts

- **NIH application ID:** 10539034
- **Project number:** 1R21NS125783-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mohamed H Farah
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $450,313
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539034

## Citation

> US National Institutes of Health, RePORTER application 10539034, Diabetic skin influences on outgrowth of human iPSC-derived sensory axons (1R21NS125783-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10539034. Licensed CC0.

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