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Bioengineering Cornea with Autologous Stem Cells

Award Number: R01EY024642
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2016
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Bioengineering Cornea with Autologous Stem Cells - This Multi-PI project combines the efforts of two research groups with different areas of expertise to address the long-term goal of developing bioengineered corneal stroma and endothelial tissues to provide therapy for individuals with corneal blindness. These tissues will be bioengineered from adult stem cells, which can be obtained from the individuals to be treated as autologous or from allogeneic cell storage since the stem cells are immunosuppressive. Over the past 5 years we have demonstrated that organization of these cells into tissues can be guided by scaffolds constructed of native extracellular matrix proteins, fabricated using a biomimetic, surface-induced assembly process. The Du Lab at the University of Pittsburgh will obtain stem cells from limbal stroma of donated human corneas. Their extensive work with these corneal stromal stem cells (CSSC) shows that they differentiate to stromal keratocytes and to corneal endothelial cells, tissues responsible for most corneal opacity. We have demonstrated that CSSC can be obtained from biopsy samples, presenting the opportunity to generate patient-specific, autologous bioengineered tissues. The Feinberg Lab at Carnegie Melon University has developed novel approach of assembling native extracellular matrix proteins to produce tissue-like scaffolding with defined 3-D architecture. Aim 1 will build on our previous work, which has showed that we can engineer spatial and biochemical cues provided by the scaffolding to generate stroma-like tissue from CSSCs that can be stacked to form multilamellar 3-D tissue similar to that of the corneal stroma. Bioengineered stroma produced in the proposed experiments will be subjected to biomechanical loading to simulate cornea development and further improve mechanical and optical properties. Function of the bioengineered stroma in lamellar keratoplasty will be evaluated in an in vivo rabbit model. Aim 2 will build on our work differentiating CSSC into endothelial cells and growing these on engineered basement membrane protein scaffolds to form polygonal monolayers that express genes typical of corneal endothelium. Previously, we demonstrated the ability to create the equivalent of Descemet's membrane to bioengineer an entire sheet of endothelium suitable for lamellar keratoplasty, but we also developed an alternative approach to engineer small patches of endothelium and deliver these via simple injection. Bioengineered endothelium produced in the proposed studies will use our newly developed “shrink-wrapping” technology to create microscale patches of corneal endothelium that can be injected into the anterior chamber for injury-free engraftment. Functionality of the constructs will be demonstrated in rabbit models in vivo, focused on boosting cell-density to improve pump function as an alternative to lamellar keratoplasty for endothelial disease. This project will build on the innovative experimental approaches we developed during the first 5 years of this project. Importantly, tissues developed and validated in vivo during this proposed study hold the potential of being advanced into clinically relevant studies to provide a novel therapeutic approach to the age-old problem of corneal blindness.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $490,603 )
2025	2025	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	8	3/20/2025	NON-COMPETING CONTINUATION	$490,603
														Subtotal = $490,603

Issue Date FY: 2024 ( Subtotal = $490,712 )
2024	2024	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	7	8/29/2024	NON-COMPETING CONTINUATION	$490,712
														Subtotal = $490,712

Issue Date FY: 2023 ( Subtotal = $490,817 )
2023	2023	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	002	6	8/15/2023	NON-COMPETING CONTINUATION	$490,817
2023	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	001	5	11/9/2022	COMPETING CONTINUATION	$1,230
2023	2019	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Vision Research	000	4	11/9/2022	NON-COMPETING CONTINUATION	-$1,230
														Subtotal = $490,817

Issue Date FY: 2022 ( Subtotal = $573,140 )
2022	2022	CARNEGIE MELLON UNIVERSITY	5000 FORBES AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	5	3/4/2022	COMPETING CONTINUATION	$573,140
														Subtotal = $573,140

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Vision Research	000	4	9/15/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	4	1/19/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $388,099 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	4	5/13/2019	NON-COMPETING CONTINUATION	$388,099
														Subtotal = $388,099

Issue Date FY: 2018 ( Subtotal = $392,697 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	3	4/13/2018	NON-COMPETING CONTINUATION	$392,697
														Subtotal = $392,697

Issue Date FY: 2017 ( Subtotal = $370,967 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	001	2	8/16/2017	NON-COMPETING CONTINUATION	$37,098
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	2	4/20/2017	NON-COMPETING CONTINUATION	$333,869
														Subtotal = $370,967

Issue Date FY: 2016 ( Subtotal = $387,134 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Vision Research	000	1	4/20/2016	NEW	$387,134
														Subtotal = $387,134

Grand Total All Awards = $3,584,169

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Bioengineering Cornea with Autologous Stem Cells

Award Number: R01EY024642

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2016

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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