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Stem cells for craniofacial bone repair and regeneration

Award Number: R01DE026936
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/30/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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Stem cells for craniofacial bone repair and regeneration - Abstract The objective of this proposal is to study newly identified stem cells essential for craniofacial skeletal development and disease. Large bone defects caused by various conditions, e.g. cancer surgery, congenital malformation, trauma and progressive deforming diseases, are major health issues. Over 2.2 million cases worldwide each year have to be addressed in the diverse fields of orthopedic, plastic and oral surgeries. The only solution for such extensive injuries or non-healing issues is to undergo a reconstructive operation. Current gold standard is to perform autograft that requires transferring bones taken from other parts of the body to the repair site. However, bone grafts are encumbered by numerous disadvantages, including donor site morbidity, limited bone supply and complications of extended operating time. The success of such reconstructions also remains highly challenging owing to a number of limitations. This leads to exploration of alternative approaches, especially stem cell-based therapy. However, the lack of knowledge regarding stem cells specific for craniofacial skeletogenesis greatly restricted further advancement. Formation of the craniofacial skeleton is mainly mediated through intramembranous ossification, a process distinct from endochondral ossification in the body skeleton. Therefore, skeletal stem cells identified for the long bone may not be suitable for reconstruction of the craniofacial bones. Using state-of-the-art mouse genetic models, a recent groundbreaking work from our laboratory has successfully isolated adult skeletal stem cells, residing in the suture mesenchyme and responsible for formation and maintenance of the craniofacial bones. Upon injury these suture stem cells react quickly and contribute directly to bone repair by replacing the damaged tissue. Animal experiments further demonstrated that the injury-induced healing process is greatly facilitated with transplantation of these naïve cells. Although our findings promise their future use in cell-based therapy and tissue engineering, there is an urgent need to understand the characteristics of these stem cells for regenerating craniofacial bone structures. Here our goal is to first perform in-depth evaluations on suture stem cells in animal models. We will further investigate their role in craniofacial bone development and disease, and elucidate the underlying skeletal repair and regeneration mediated by suture stem cells. We will emphasize characterizing their innate ability to regrow craniofacial bone structures. Next, to move a step closer to clinical applications, we plan to study the corresponding human stem cells and characterize their self-renewal, clonal expansion, proliferation, and differentiation abilities. This proposal has outstanding potential to advance the field of regenerative medicine. By studying human cells, we are closer to translating our findings for clinical use, improving reconstructive surgical repair, and maximizing the benefits of regenerative medicine.


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: 2024 ( Subtotal = $0 )
2024	2022	ADA FORSYTH INSTITUTE, INC.	245 1ST ST 17TH FLOOR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	5	6/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $657,798 )
2022	2022	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	000	5	5/19/2022	NON-COMPETING CONTINUATION	$657,798
														Subtotal = $657,798

Issue Date FY: 2021 ( Subtotal = $664,443 )
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	003	4	9/28/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$275,963
2021	2021	FORSYTH DENTAL INFIRMARY FOR CHILDREN	245 FIRST ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Oral Diseases and Disorders Research	001	4	8/23/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$664,443
2021	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	002	3	9/28/2021	NON-COMPETING CONTINUATION	-$275,963
2021	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	3	8/20/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $664,443

Issue Date FY: 2020 ( Subtotal = $514,192 )
2020	2020	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	3	5/28/2020	NON-COMPETING CONTINUATION	$514,192
														Subtotal = $514,192

Issue Date FY: 2019 ( Subtotal = $514,192 )
2019	2019	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	2	5/8/2019	NON-COMPETING CONTINUATION	$514,192
														Subtotal = $514,192

Issue Date FY: 2018 ( Subtotal = $514,192 )
2018	2018	UNIVERSITY OF ROCHESTER	500 JOSEPH C WILSON BLVD	ROCHESTER	NY	14627	MONROE	USA	Oral Diseases and Disorders Research	000	1	5/31/2018	NEW	$514,192
														Subtotal = $514,192

Grand Total All Awards = $2,864,817

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Stem cells for craniofacial bone repair and regeneration

Award Number: R01DE026936

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/30/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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