You are here

Small-molecule combinationsexpand hematopoietic stem cell ex vivo and in vivo

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HL145877-01A1
Agency Tracking Number: R41HL145877
Amount: $203,101.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NHLBI
Solicitation Number: PA18-575
Solicitation Year: 2018
Award Year: 2019
Award Start Date (Proposal Award Date): 2019-09-15
Award End Date (Contract End Date): 2021-07-31
Small Business Information
3401 GRYS FERRYA VE, BLDG 176 1013, Philadelphia, PA, 19103-1031
DUNS: 080743097
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (215) 707-2647
Business Contact
Phone: (610) 864-6283
Research Institution
PHILADELPHIA, PA, 19122-6003
 Nonprofit college or university
Small molecule combinations expand hematopoietic stem cell ex vivo and in vivo Abstract Hematopoietic stem cellsHSCsare featured by their self renewal potential and ability to differentiate into multiple blood lineagesHematopoietic stem cell transplantHSCTis a mainstay of life saving therapy for hematopoietic malignancies and hypoproliferative disordersThe use of noninvasively accessible umbilical cord bloodUCBderived HSCs provides many advantages over bone marrow and peripheral blood HSCincluding less stringent requirement for human leukocyte antigenHLAmatchdecreased risk of graft versushost diseaseGVHDetcHoweverlimited cell dose in a UCB unit may lead to significant problems such as delayed engraftmentengraftment failureand severe infectious complicationsThe expansion of HSCs from UCB has remained an important goal to develop advanced cell therapies for enhancing transplantation efficacy and providing potential cure for various hematological diseasesRecent studies have achieved ex vivo expansion of HSCs using cytokine cocktails combined with small moleculesincluding pyrimidoindole derivativeUMaryl hydrocarbon receptor antagonistSRThe major disadvantage with these approaches is that it is only effective in the presence of high concentration of cytokinesCytokines have been known to induce differentiation and affect the function of primitive HSCthey might have long term deleterious effect on humans due to skewed reconstitution of the hematopoietic systemThe small molecule combinations with minimal cytokines would be ideal for clinical applicationsOur published studies demonstrated a combination of two inhibitorsiallows the ex vivo maintenance of human and mouse long term HSCs and doing so under cytokine free conditionThe combination of two clinical drugslithium plus rapamycinleads to increase of long term mouse HSCs in vivoIn our recent studieswe found thati works synergistically with SRunder low cytokine conditionsignificantly expanded long term functional HSC ex vivoIn this projectwe will carry out studies to optimize culture condition of small molecule combination regimensFurthermorewe will test and optimize the in vivo expansion methodwhich will greatly improve the successful rate of HSC transplantationOur major goal is to develop new clinical protocols for expanding functional UCBderived HSCs for therapeutic applications Narrative All blood cells arise from a common precursor called the hematopoietic stem cellHSCHSC is able to differentiate into mature blood cells as well as to replenish the pool of HSCsClinicallyHSCs are key for bone marrow transplantation for treating leukemia and other blood diseasesBut the number of HSC is limited in cord blood for transplantationThe proposal aims to develop methods that can be used to improve the outcome of clinical bone marrow transplantationsThe academic partner has developed a small molecule combinationi SRwith the minimal cytokines to expand HSC ex vivoThe small business partner is experienced in stem cell based therapyTogether we are aiming to test if a commercial small molecule combination regimen for expanding HSC ex vivo and in vivo is feasible and to transfer this technology to the small business partner for further clinical development and applicationThis new technology will significantly advance HSC transplantation and reduce the morbidity and mortality of this life saving clinical procedure

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

US Flag An Official Website of the United States Government