Research

Research Division

The Research Division of the Hoxworth Blood Center is one of the leaders in the coordination of research projects developed for the advancement of transfusion medicine including clinical trials for transfusion medicine-related products. These projects encompass a broad range of studies including analysis of red blood cells, platelets, plasma, and evaluation of techniques that improve the quality of blood components during storage.

The research program has multiple areas of interest including basic translational and clinical research.  Currently, we are developing new methods to study the basic biology and regulation of adult stem cell proliferation and differentiation. Our aim is to link these studies with bioengineering processes that might allow us to develop blood products ex vivo from adult stem cells.
 
Our goal is to link basic research with clinical care leading to improved methods that ensure the quality, safety, and efficacy of transfusion therapies.
 
There are two major areas of focus in our laboratories:

1. Clinical Research in Transfusion Medicine
2. Stem Cell Biology  (hematopoietic and mesenchymal/stromal).

Clinical Research in Transfusion Medicine
 
The Research department assists companies with licensing studies for new products. Some of the biomedical companies we collaborate with include: Caridian BCT;  Caridian BCT Biotechnologies; Fenwal Division; Cerus Corporation; MacoPharma/United Pharma;  Hemerus Medical, LLC; Greiner Corporation; ZymeQuest Inc.; Pall Medical; Alpha Bio Groups; Haemonetics Corp. and HemCon Medical Technologies. 

Current technologies:

1. Radioisotope labeling methods for measurement of red cell recovery and survival using chromium-51 and technetium-99m.
2. Radioisotope labeling methods for measurement of platelet recovery and survival using chromium-51 and indium-111.
3. Morphologic and functional tests of red blood cells including: adenosine 5’ triphosphate (ATP), 2,3 diphosphoglycerate (DPG), supernatant hemoglobin, hemolysis, osmotic fragility, blood gases, glucose, sodium, potassium, lactate, morphology, rejuvenation of ATP and 2,3 DPG and flow-cytometric measurement of microparticles (microvesicles) and annexin V.
4. Evaluation of leukoreduced products including flow-cytometric, low event leukocyte counting and percent cell loss.
5. Morphologic and functional platelet test including: hypotonic shock response, extent of shape change, morphology, aggregation, lactate dehydrogenase and flow-cytometric measurement of CD62-P (P-selectin, annexin V and microparticles.
6. Plasma analysis including: protein and coagulation assays.
7. Evaluation of different automated blood collection systems/technologies.
8. Pathogen reduction studies in blood components.

Compliance:
All studies are reviewed and approved by the Institutional Review Board of the University of Cincinnati Medical Center and Radiation Safety where applicable. Current Good Manufacturing Practices are followed in performance of all procedures, and the laboratory meets the standards of all sponsors as determined by on-site inspections.


Staff:
The staff has over 60 years of cumulative research experience. They are well trained in the use of in vitro and in vivo techniques and radioisotope labeling procedures. They perform and evaluate new procedures and products related to the collection, processing, and storage of red blood cells and platelets as required by the FDA for licensing new products.
 

Selected Publications:

1. Successful in vivo recovery and extended storage of additive solution (AS)-5 red blood cells after deglycerolization and resuspension in AS-3 for 15 days with an automated closed system. Bandarenko N, Cancelas JA, Snyder E, Haya SN, Rugg N, Corda T, Joines AD, Gormas JF, Pratt PG, Kowalskya R, Rose M, Rose L, Foley J, Popovsky M. Transfusion 2007 Apr;47:680-6.
2. Evaluation of proposed FDA criteria for the evaluation of radio-labeled red cell recovery trials. Dumont LJ, Aubuchon JP, for the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. (Cancelas J, Rugg N, Hoxworth Blood Center, participating laboratory). Transfusion 2008 Jun 48(6):1053-60.

View Recent Publications

Stem Cell Biology
(hematopoietic and mesenchymal/stromal)
 
Our laboratory focuses on the study of blood-forming cells during the process of adult hematopoiesis. Billions of cells are produced daily in a crucially regulated fashion to maintain homeostatic cell counts in circulation and provide all functional blood cell types (neutrophils, eosinophils, basophils, monocytes/macrophages, platelets, and erythrocytes) and other tissue cells (mast cells and osteoclasts). Adult hematopoiesis is located in the bone marrow and is initiated by hematopoietic stem cells (HSC), which are able to self-renew and differentiate into all functional types of blood cells. HSC attract clinical interest because of their potential use in stem cell and gene therapy.
 
Despite the advance in the understanding of how stem cells proliferate and differentiate, we do not fully understand the mechanisms that control the bone marrow stem cell compartment. One of the major challenges has been to understand the role of the "bone marrow microenvironment" in the regulation of the proliferation and differentiation of HSC. Although poorly characterized, this microenvironment is composed of stromal cells, including myofibroblasts, adipocytes, and osteoblasts, that originate from mesenchymal progenitors –MSCs-, hematopoietic-derived cells such as lymphocytes and macrophages, and of extracellular matrix proteins (collagen, fibronectin, vitronectin, laminin, hemonectin, among others). The stroma provides growth factors, chemoattractants, anchorage, and scaffolding for the correct development of hematopoiesis.

Molecular Mechanisms Controlling HSC Engraftment and Mobilization - Selected Publications:

1. Cdc42 critically regulates the balance between myelopoiesis and erthropoiesis. Yang L, Wang L, Kalfa TA, Cancelas JA, Shang S, Pushkaran S, Mo J, Williams DA, Zheng Y.  Blood 2007 Dec 1;110(12):3853:-7.
2. Rac GTPases differentially integrate signals regulating hematopoietic stem cell localization. Cancelas JA, Lee AW, Prabhakar R, Stringer KF, Zheng Y, Williams DA.  Nat Med 2005 Aug; 11(8):886-91.

View Recent Publications

Extrinsic and Small GTPase Signaling in Cancer Stem Cells and Progenitors - Selected Publications:

1. FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome. Yamada, Y, Sanchez-Aguilera A, Brandt EB, McBride M, Al-Moamen NJ, Finkelman FD, Williams DA, Cancelas JA, Rothenberg ME.  Blood 2008 Sep 15;112(6):2500-7.
2. Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative disease.  Thomas EK, Cancelas JA, Chae HD, Cox AD, Keller PJ, Perrotti D, Neviani P, Druker BJ, Setchell, KD, Zheng Y, Harris CE, Williams DA.  Cancer Cell 2007 Nov;12(5):467-78.

View Recent Publications

For additional information about related research projects, select the following links:

Research Publications

Patents

Grant Support

Division of Experimental Hematology of Cincinnati Children’s Hospital Medical Center.

Updated 3/9/09

Slideshow: Research Findings