Regulation of platelet production and activation
For patients suffering from thrombocytopenia, transfusion of allogeneic platelets can be lifesaving. More than 2 million units are required for transfusion every year, but obtaining sufficient sources of donor platelets is challenging. Additionally, platelet units have a limited shelf life and carry the risk of viral or bacterial infection. New methods to expand platelets in vitro would circumvent these limitations, improve our ability to meet clinical demands, lower the cost of unit safety testing, greatly enhance transfusion medicine and assist in patient treatment. Various formulations of culture conditions have been investigated for platelet expansion, but resulted in limited expansion of platelets with incomplete functionality. We identified an important role for MSCs in enhancing platelet formation in vitro and importantly, producing platelets with a low basal activation state. In my lab, we are investigating the mechanism by which MSCs and other niche cells in the bone marrow may improve platelet formation in MKs and prevent activation of platelets. Using this knowledge, we are investigating methods for expanding platelets ex-vivo and developing cutting-edge tools to assist with this process.
Microenvironmental regulation of hematopoietic stem and progenitor cells
Hematopoietic stem cells (HSCs) are responsible for producing all of the blood cell lineages throughout life. Within the bone marrow, a closely regulated microenvironment, or niche, controls the quiescence, proliferation, and differentiation of HSCs. While significant progress has been made to understand the key cellular players responsible for regulating the hematopoietic niche, many questions remain. We are interested in understanding how the hematopoietic stem cell microenvironment is affected under steady state and conditions of hematological malignancy.
• NIH P01 HL149626 Mendelson Co-I (An PI, Project 4) 07/20/2020 – 06/30/2025 “Hemolysis and the Hematopoietic Niche”
Education and Training
- Albert Einstein College of Medicine
- Ph.D. Columbia University; Biomedical Engineering
- M.E. Cornell University; Biomedical Engineering
- B.S. Cornell University; Biological Engineering
Beri D, Singh M, Rodriguez M.A., Barbu-Stevanovic M, Rasquinha G, Mendelson A, An X, Manwani D, Yazdanbakhsh K, Lobo C.A. Elucidating Parasite and Host Cell Factors Enabling Babesia Infection in Sickle Red Cells under Hypoxic/Hyperoxic Conditions. Blood Adv. 2022 Aug 17;bloodadvances.2022008159.
Tang A, and Mendelson A. Recent lessons learned for ex-vivo platelet production. Curr Opin Hematol. 2021 Nov 1; 28(6):424-430.
Zhang H, Wang S, Liu D, Gao C, Han Y, Guo X, Qu X, Li W, Zhang S, Geng J, Zhang L, Mendelson A, Yazdanbakhsh K, Chen L, An X. EpoR-tdTomato-Cre mice enable identification of EpoR expression in subsets of tissue macrophages and hematopoietic cells. Blood. 2021 Nov 18; 138(20): 1986-1997.
Tang, A, Strat, AN, Rahman, M, Zhang, H, Bao, W, Liu, Y, Shi, D, An, X, Manwani, D, Shi, P, Yazdanbakhsh, K, Mendelson, A. Murine bone marrow mesenchymal stromal cells have reduced hematopoietic maintenance ability in sickle cell disease. Blood. 2021 Dec 16;138(24):2570-2582.
Vinchi F, Mendelson A, Yazdanbakhsh K, An X. Uncovering the Bone Marrow Microenvironment Cell by Cell. Hemasphere. 2019 Dec 9;3(6):e299.
Mendelson A, Strat AN, Bao W, Rosston P, Fallon G, Ohrn S, Zhong H, Lobo C, An X, Yazdanbakhsh K. Mesenchymal stromal cells lower platelet activation and assist in platelet formation in vitro. JCI Insight. 2019 Aug 22;4(16).
Li W, Wang Y, Zhao H, Zhang H, Xu Y, Wang S, Guo X, Huang Y, Zhang S, Han Y, Wu X, Rice CM, Huang G, Gallagher PG, Mendelson A, Yazdanbakhsh K, Liu J, Chen L, An X. Identification and transcriptome analysis of erythroblastic island macrophages. Blood. 2019 Aug 1;134(5):480-491.
Liu Y, Zhong H, Bao W, Mendelson A, An X, Shi P, Chou ST, Manwani D, Yazdanbakhsh K. Patrolling monocytes scavenge endothelial-adherent sickle RBCs: a novel mechanism of inhibition of vaso-occlusion in SCD. Blood. 2019 Aug 15;134(7):579-590.
Liu Y, Zhong H, Vinchi F, Mendelson A, Yazdanbakhsh K. Patrolling monocytes in sickle cell hemolytic conditions. Transfus Clin Biol. 2019 May;26(2):128-129.
Yi W, Bao, W, Rodriguez M, Liu Y, Singh M, Ramlall V, Cursino-Santos J, Zhong H, Wright G.J., Mendelson A, An X, Lobo C and Yazdanbakhsh K. Robust adaptive immune response against Babesia microti infection marked by low parasitemia in a murine model of sickle cell disease. Blood Advances. 2018. Dec 11; 2(23): 3462–3478.
Liu Y, Jing F, Yi W, Mendelson A, Shi P, Walsh R, Friedman DF, Minniti C, Manwani D, Chou ST, and Yazdanbakhsh K. HO-1hi Patrolling Monocytes Protect against Vaso-occlusion in Sickle Cell Disease. Blood. 2018 Apr 5; (131) 14: 1600-1610.
Khan JA, Mendelson A, Kunisaki Y, Kou Y, Arnal A, Pinho A, Ciero P, Nakahara F, Ma’ayan A, Bergman A, Merad M and Frenette PS. Fetal liver hematopoietic stem cell niches associate with portal vessels. Science. 2016 Jan 8; 351(6269) 176-80.
Mendelson A and Frenette P. Hematopoietic stem cell niche maintenance during homeostasis and Regeneration. Nature Medicine. 2014. 20(8): 833-846.
Mizoguchi T, Ahmed J, Kunisaki Y, Pinho S, Mendelson A, Ono N, Kronenberg HM, Frenette PS. Osterix marks distinct waves of primitive and definitive stromal progenitors during bone marrow development. Developmental Cell. 2014. May 12: 29(3): 340-9.
Mendelson A, Ahn JM, Paluch K, Embree MC, Mao JJ. Engineered nasal cartilage by cell homing: A model for augmentative and reconstructive rhinoplasty. Plastic and Reconstructive Surgery. 2014, June; 133(6): 1344-53.
Mendelson A, Cheung YK, Paluch K, Chen M, Kong K, Tan J, Dong Z, Sia SK, Mao JJ. Competitive Stem Cell Recruitment by Multiple Cytotactic Cues. Lab on a Chip. 2013, March 21, 13(6): 1156-64.
Nie H, Lee CH, Tan J, Lu C, Mendelson A, Chen M, Embree MC, Kong K, Shah B, Wang S, Cho S, Mao JJ. Musculoskeletal tissue engineering by endogenous stem/progenitor cells. Cell & Tissue Research. 2012 Mar, 347 (3): 665-76.
Embree MC, Mendelson A, Lu C, Lee CH, Mao JJ. Regeneration: endogenous stem cells vs. transplanted stem cells. Biomaterials and Regenerative Medicine. Ma P (Ed). Cambridge University Press, 2012.
Mendelson A, Frank E, Allred C, Jones E, Chen M, Zhao W, Mao JJ. Chondrogenesis by chemotactic homing of synovium, bone marrow, and adipose stem cells in vitro. FASEB J, 2011. Oct; 25(10):3496-504.
Mendelson A, Lee CH, Mao JJ. Cartilage Regeneration With and Without Cell Transplantation. Stem Cell Bioengineering and Tissue Engineering Microenvironment. Prakash S, Shum-Tim D (Eds). World Scientific Publishing, 2011. 339-350.
Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet, 2010. Aug 7; 376(9739):440-8.
Albrecht DR, Underhill GH, Resnikoff J, Mendelson A, Bhatia SN, Shah JV. Microfluidics-integrated time-lapse imaging for analysis of cellular dynamics. Integr Biol (Camb). 2010 June; 2(5-6):278-87.
Mendelson A, Lee CH, Mao JJ. Cartilage regeneration by cell homing. 3-D Tissue Engineering. Yarmush ML, Langer RS (Eds). Artech House, 2009
Albrecht DR, Underhill GH, Mendelson A, Bhatia SN. Multiphase electropatterning of cells and biomaterials. Lab Chip. 2007 June; 7(6):702-9.
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