Award Abstract # 2305874
Collaborative Research: Investigating the role and interplay of microenvironment, manufacturing, and metabolism on MSC production of extracellular vesicles

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: TRUSTEES OF UNION COLLEGE IN THE TOWN OF SCHENECTADY IN THE STATE OF NEW YORK
Initial Amendment Date: June 5, 2023
Latest Amendment Date: June 5, 2023
Award Number: 2305874
Award Instrument: Continuing Grant
Program Manager: Steven Peretti
speretti@nsf.gov
 (703)292-4201
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: June 15, 2023
End Date: May 31, 2026 (Estimated)
Total Intended Award Amount: $86,662.00
Total Awarded Amount to Date: $56,788.00
Funds Obligated to Date: FY 2023 = $56,788.00
History of Investigator:
  • Sudhir Khetan (Principal Investigator)
    khetans@union.edu
Recipient Sponsored Research Office: Union College
807 UNION ST
SCHENECTADY
NY  US  12308-3256
(518)388-6101
Sponsor Congressional District: 20
Primary Place of Performance: Union College
807 UNION ST
SCHENECTADY
NY  US  12308-3256
Primary Place of Performance
Congressional District:
20
Unique Entity Identifier (UEI): HE9HQBNZHHB5
Parent UEI:
NSF Program(s): Cellular & Biochem Engineering
Primary Program Source: 01002324DB NSF RESEARCH & RELATED ACTIVIT
01002526DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 1757, 1491
Program Element Code(s): 149100
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

Mesenchymal stromal cells (MSCs) are isolated from bone marrow and fat cells. While they are not stem cells, they exhibit a similar ability to differentiate into many types of cells. That ability forms the basis for developing treatments for a variety of diseases. MSCs also generate extracellular vesicles (EVs). The EVs transport bioactive molecules that prompt cellular-level responses. It is difficult to manufacture EVs reproducibly. This limits its current therapeutic potential. Changes in local conditions impact MSC-EV production and function. Understanding those impacts is the focus of this project. The project will also promote STEM participation of students from underrepresented groups.

Many challenges contribute to the lack of successful MSC-EV clinical translation. MSC heterogeneity is a key issue. There are no effective critical quality attributes (CQAs) that predict how a given batch of EVs will perform. There are also no standardized manufacturing approaches for EVs. In addition, there is a knowledge gap regarding the effects of scaling EV manufacturing with respect to 2D vs. 3D environments. The overall goals of this project are to understand how 3D structure affects EV production and to identify metabolic pathways controlling this response. To accomplish these goals, the project team will: 1) investigate the effects of 3D hydrogel microenvironments on EV function, 2) determine the effects of manufacturing strategies on EVs, and 3) define metabolic changes associated with EV production. It is anticipated that the mechanisms identified will have relevance for MSC-EVs for different therapeutic applications and for EVs generated by other cell types.

This project is jointly supported by the Cellular and Biochemical Engineering Program in ENG/CBET and the Systems and Synthetic Biology Program in BIO/MCB.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

Please report errors in award information by writing to: awardsearch@nsf.gov.

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