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AMINE OXIDASE-DEPLETED CELL CULTURE MEDIA FOR STEM CELLS

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
19092
Program Year/Program:
1994 / SBIR
Agency Tracking Number:
19092
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Hipple Cancer Research
4100 S Kettering Boulevard Dayton, OH 45439
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 2
Fiscal Year: 1994
Title: AMINE OXIDASE-DEPLETED CELL CULTURE MEDIA FOR STEM CELLS
Agency: HHS
Contract: N/A
Award Amount: $512,000.00
 

Abstract:

A FAMILY OF PLASMA ENZYMES NAMED AMINE OXIDASES CONTRIBUTE TO A LACK OF SURVIVAL OF HEMATOPOIETIC PROGENITOR CELLS IN VITRO BY OXIDIZING THE AMINES RELEASED INTO THE MEDIUM INTO CYTOTOXIC AND MUTAGENIC HYDROGEN PEROXIDE AND ALDEHYDES. THIS SHORT-TERM TOXICITY MANIFESTS AS LOW CLONING EFFICIENCIES. INHIBITORS OF PLASMA AMINE OXIDASES PREVENT THESE TOXIC EFFECTS AND INCREASE CLONING EFFICIENCIES FOR MURINE CFU-ERYTHROID AND CFU-GRANULOCYTE/MACROPHAGE. THESE INHIBITORS CAN SUBSTITUTE FOR 2-MERCAPTOETHANOL IN THE CFU-E ASSAY, PROVIDING AN EXPLANATION FOR THE STIMULATORY EFFECTS OF THIOLS ORIGINALLY DISCOVERED BY ISCOVE. HOWEVER, THESE ENZYME INHIBITORS ARE TOXIC TO HUMAN CELLS, SO OTHER APPROACHES ARE NEEDED TO ELIMINATE AMINE OXIDASE TOXICITY. SERUM-FREE MEDIA DO NOT NECESSARILY CIRCUMVENT THIS PROBLEM, BECAUSE MANY "PURIFIED" PROTEINS OR ADDITIVES REQUIRED FOR THESE MEDIA CONTAIN AMINE OXIDASES AS CONTAMINANTS. THESE ENZYMES ALSO CAUSE LONG-TERM TOXICITY, SUCH AS THE CRISIS OF SPONTANEOUS TRANSFORMATION IN CULTURES OF MOUSE EMBRYO CELLS. THESE DATA SUGGEST THAT AMINE OXIDASE TOXICITY IS UBIQUITOUS IN VITRO, AND, FURTHERMORE, THAT THE DEVELOPMENT OF CULTURE SUPPLEMENTS DEVOID OF AMINE OXIDASES MAY FACILITATE ADVANCES IN THE STUDY AND MANIPULATION OF STEM CELLS EX VIVO. IN PHASE I, WE WILL DETERMINE WHICH PLASMA AMINE OXIDASES CAUSE TOXICITY. IN PHASE II, WE WILL DEVELOP TECHNOLOGY TO ELIMINATE DELETERIOUS AMINE OXIDASES FROM THE CULTURE SUPPLEMENTS, CONFIRM THAT THEIR ELIMINATION PREVENTS SHORT- AND LONG-TERM TOXICITIES, AND APPLY THIS NEW CELL CULTURE TECHNOLOGY TOWARD THE DEVELOPMENT OF STEM CELL LINES FROM NORMAL AND MALIGNANT HUMAN BONE MARROW, BREAST, PROSTATE, AND LYMPH NODE, INCLUDING LYMPHOMAS. SUCH CELL LINES MAY PROVE VALUABLE FOR CARCINOGENESIS AND MUTAGENESIS STUDIES, FOR IN VITRO ASSAYS FOR IDENTIFYING NEW ANTI-CANCER DRUGS, AND FOR STABILIZING THE GENOME OF HYBRIDOMAS (CURRENTLY CULTURED IN 2-MERCAPTOETHANOL). THE TECHNOLOGY HOLDS PROMISE FOR A BASE FROM WHICH MANY OF THE IN VITRO GOALS OF "HEALTHY PEOPLE-2000" MAY BE ACHIEVED.

Principal Investigator:

Kunthavi Natarajan
5132997120

Business Contact:

Small Business Information at Submission:

Hipple Cancer Research Center
4100 South Kettering Boulevard Dayton, OH 45439

EIN/Tax ID:
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No