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Novel Highly Regenerative and Scalable Progenitor Cell Exosomes for Treating Peripheral Artery Disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL170875-01
Agency Tracking Number: R41HL170875
Amount: $340,956.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-01
Award End Date (Contract End Date): 2024-08-31
Small Business Information
Alameda, CA 94501
United States
DUNS: 080918820
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (510) 457-5192
Business Contact
Phone: (510) 671-8381
Research Institution
PALO ALTO, CA 94304-1207
United States

 Domestic Nonprofit Research Organization

Peripheral artery disease (PAD) is associated with vascular obstructions in the extremities, leading to intermittent
claudication, ischemic ulcers, leg pain at rest, and amputation. In the US, approximately 6.5 million people have
peripheral artery disease (PAD),
affecting 12-20% of people over 60 years of age
. Current cell therapies to
restore limb perfusion have shown only moderate benefits due to poor transplant cell survival and inadequate
pro-angiogenic cues. Therefore, there is a critical need for alternative treatments for PAD therapy. Recently,
therapy using mesenchymal stem cell (MSCs)-derived exosomes has been recognized as a promising, cell-free
treatment in various diseases, including PAD. However, MSCs are heterogeneous and do not scale well, thus,
limiting their usefulness as a reliable source of exosomes for commercial scale development and clinical
application. We at AgeX Therapeutics have previously shown that our highly regenerative, proprietary
PureStem® progenitor cells, which are at an early developmental state, produce highly angiogenic exosomes.
Thus, we propose to overcome the current exosome production limitations by using AgeX’s highly scalable
PureStem® human pluripotent stem cell-derived cell lines as a source of allogeneic PAD therapy. A key rationale
for using exosomes is that they have low immunogenicity, which means they are not likely to cause undesirable
immune responses, and they are non-replicative, which obviates many of the risks associated with cell therapy.
Since exosomes mediate intercellular communication, instead of administering cells, we can use PureStem
angiogenic exosomes in a murine model of PAD to improve limb revascularization and blood perfusion. Moreover,
exosomes are likely to be more cost-effective to produce and more convenient to use and store.
The goal of this STTR Phase I proposal is to demonstrate the therapeutic feasibility of exosomes to improve
angiogenic function in a mouse hindlimb ischemia model. First, we will establish two lead angiogenic exosome
production cell lines and produce GMP-compatible PureStem® exosomes in vitro by assessing lines based on
exosome output, exosome angiogenic activity, and exosome scalability and stability. We will then test the two
selected PureStem exosome lines in a hindlimb ischemia mouse model to validate their therapeutic efficacy in
vivo. Evidence of in vivo feasibility in our well-established PAD animal model using exosomes from a scalable
PureStem cell line will pave the way for further preclinical development and IND, thus enabling studies for a
prospective STTR Phase II. Taken together, we anticipate the therapeutic potential for PureStem exosomes to
provide an innovative, cost-effective, and convenient “off-the-shelf” regenerative stem cell-derived therapy for

* Information listed above is at the time of submission. *

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