Research

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Juan  Melero-Martin, PhD

Juan Melero Martin
Lab:
Melero-Martin Laboratory
Department:
Cardiac Surgery Research
Hospital Title:
Staff Scientist
Academic Title:
Assistant Professor, Harvard Medical School
Research Focus Area:
Tissue EngineeringCell therapyVascular biology

Research Overview

Stem cell transplantation and tissue engineering hold great promise in regenerative medicine. However, generating tissues with stable functional vascular beds remains a major challenge. Our laboratory is interested in understanding mechanisms of vascular network formation using human stem and progenitor cells. We specialize in the biology and therapeutic potential of human circulating Endothelial Colony-Forming Cells. Current projects in the lab are focused on:

  • Endothelial colony-forming cells (ECFCs) biology
  • Bioengineering vascular networks
  • Genetically-engineered vasculature for protein drug delivery

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About Juan Melero-Martin

Dr. Melero-Martin graduated in Chemical Engineering from University of Seville, Spain, in 1998. After working three years in industry, he went on to earn a PhD in biochemical engineering from the University of Birmingham, UK in 2005. Dr. Melero-Martin's doctoral research focused on tissue engineering and was sponsored by Smith & Nephew. From 2005 to 2008, he trained as a post-doctoral fellow in the Vascular Biology Program at Boston Children's Hospital. He joined the Department of Cardiac Surgery at Children's Hospital in 2008. In 2009, he received a K99/R00 Pathway to Independence Award from the NIH.

Publications

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  1. Barati D, Shariati SR, Moeinzadeh S, Melero-Martin JM, Khademhosseini A, Jabbari E. Spatiotemporal release of BMP-2 and VEGF enhances osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells co-encapsulated in a patterned hydrogel. J Control Release. 2016 Feb 10; 223:126-36.
  2. Kuo KC, Lin RZ, Tien HW, Wu PY, Li YC, Melero-Martin JM, Chen YC. Bioengineering vascularized tissue constructs using an injectable cell-laden enzymatically crosslinked collagen hydrogel derived from dermal extracellular matrix. Acta Biomater. 2015 Nov; 27:151-66.
  3. Chuang CH, Lin RZ, Tien HW, Chu YC, Li YC, Melero-Martin JM, Chen YC. Enzymatic regulation of functional vascular networks using gelatin hydrogels. Acta Biomater. 2015 Jun; 19:85-99.
  4. Dunleavey JM, Xiao L, Thompson J, Kim MM, Shields JM, Shelton SE, Irvin DM, Brings VE, Ollila DW, Brekken RA, Dayton PA, Melero-Martin JM, Dudley AC. Vascular channels formed by subpopulations of PECAM1+ melanoma cells. Nat Commun. 2014; 5:5200.
  5. Liu Q, Huang X, Oh JH, Lin RZ, Duan S, Yu Y, Yang R, Qiu J, Melero-Martin JM, Pu WT, Zhou B. Epicardium-to-fat transition in injured heart. Cell Res. 2014 Nov; 24(11):1367-9.
  6. Lin RZ, Hatch A, Antontsev VG, Murthy SK, Melero-Martin JM. Microfluidic capture of endothelial colony-forming cells from human adult peripheral blood: phenotypic and functional validation in vivo. Tissue Eng Part C Methods. 2015 Mar; 21(3):274-83.
  7. Lin CI, Merley A, Sciuto TE, Li D, Dvorak AM, Melero-Martin JM, Dvorak HF, Jaminet SC. TM4SF1: a new vascular therapeutic target in cancer. Angiogenesis. 2014 Oct; 17(4):897-907.
  8. Lin RZ, Moreno-Luna R, Li D, Jaminet SC, Greene AK, Melero-Martin JM. Human endothelial colony-forming cells serve as trophic mediators for mesenchymal stem cell engraftment via paracrine signaling. Proc Natl Acad Sci U S A. 2014 Jul 15; 111(28):10137-42.
  9. Muñoz-Hernandez R, Miranda ML, Stiefel P, Lin RZ, Praena-Fernández JM, Dominguez-Simeon MJ, Villar J, Moreno-Luna R, Melero-Martin JM. Decreased level of cord blood circulating endothelial colony-forming cells in preeclampsia. Hypertension. 2014 Jul; 64(1):165-71.
  10. Moreno-Luna R, Muñoz-Hernandez R, Lin RZ, Miranda ML, Vallejo-Vaz AJ, Stiefel P, Praena-Fernández JM, Bernal-Bermejo J, Jimenez-Jimenez LM, Villar J, Melero-Martin JM. Maternal body-mass index and cord blood circulating endothelial colony-forming cells. J Pediatr. 2014 Mar; 164(3):566-71.
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  12. Lin RZ, Chen YC, Moreno-Luna R, Khademhosseini A, Melero-Martin JM. Transdermal regulation of vascular network bioengineering using a photopolymerizable methacrylated gelatin hydrogel. Biomaterials. 2013 Sep; 34(28):6785-96.
  13. Lin RZ, Moreno-Luna R, Muñoz-Hernandez R, Li D, Jaminet SC, Greene AK, Melero-Martin JM. Human white adipose tissue vasculature contains endothelial colony-forming cells with robust in vivo vasculogenic potential. Angiogenesis. 2013 Oct; 16(4):735-44.
  14. Wagner M, Bjerkvig R, Wiig H, Melero-Martin JM, Lin RZ, Klagsbrun M, Dudley AC. Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis. Angiogenesis. 2012 Sep; 15(3):481-95.
  15. Lin RZ, Moreno-Luna R, Zhou B, Pu WT, Melero-Martin JM. Equal modulation of endothelial cell function by four distinct tissue-specific mesenchymal stem cells. Angiogenesis. 2012 Sep; 15(3):443-55.
  16. Chen YC, Lin RZ, Qi H, Yang Y, Bae H, Melero-Martin JM, Khademhosseini A. Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels. Adv Funct Mater. 2012 May 23; 22(10):2027-2039.
  17. Lin RZ, Melero-Martin JM. Fibroblast growth factor-2 facilitates rapid anastomosis formation between bioengineered human vascular networks and living vasculature. Methods. 2012 Mar; 56(3):440-51.
  18. Lin RZ, Dreyzin A, Aamodt K, Li D, Jaminet SC, Dudley AC, Melero-Martin JM. Induction of erythropoiesis using human vascular networks genetically engineered for controlled erythropoietin release. Blood. 2011 Nov 17; 118(20):5420-8.
  19. Zhou B, Honor LB, Ma Q, Oh JH, Lin RZ, Melero-Martin JM, von Gise A, Zhou P, Hu T, He L, Wu KH, Zhang H, Zhang Y, Pu WT. Thymosin beta 4 treatment after myocardial infarction does not reprogram epicardial cells into cardiomyocytes. J Mol Cell Cardiol. 2012 Jan; 52(1):43-7.
  20. Lin RZ, Melero-Martin JM. Bioengineering human microvascular networks in immunodeficient mice. J Vis Exp. 2011; (53):e3065.
  21. Zhou B, Honor LB, He H, Ma Q, Oh JH, Butterfield C, Lin RZ, Melero-Martin JM, Dolmatova E, Duffy HS, Gise Av, Zhou P, Hu YW, Wang G, Zhang B, Wang L, Hall JL, Moses MA, McGowan FX, Pu WT. Adult mouse epicardium modulates myocardial injury by secreting paracrine factors. J Clin Invest. 2011 May; 121(5):1894-904.
  22. Melero-Martin JM, Dudley AC. Concise review: Vascular stem cells and tumor angiogenesis. Stem Cells. 2011 Feb; 29(2):163-8.
  23. Allen P, Melero-Martin J, Bischoff J. Type I collagen, fibrin and PuraMatrix matrices provide permissive environments for human endothelial and mesenchymal progenitor cells to form neovascular networks. J Tissue Eng Regen Med. 2011 Apr; 5(4):e74-86.
  24. Lin RZ, Dreyzin A, Aamodt K, Dudley AC, Melero-Martin JM. Functional endothelial progenitor cells from cryopreserved umbilical cord blood. Cell Transplant. 2011; 20(4):515-22.
  25. Melero-Martin JM, De Obaldia ME, Allen P, Dudley AC, Klagsbrun M, Bischoff J. Host myeloid cells are necessary for creating bioengineered human vascular networks in vivo. Tissue Eng Part A. 2010 Aug; 16(8):2457-66.
  26. Hjortnaes J, Gottlieb D, Figueiredo JL, Melero-Martin J, Kohler RH, Bischoff J, Weissleder R, Mayer JE, Aikawa E. Intravital molecular imaging of small-diameter tissue-engineered vascular grafts in mice: a feasibility study. Tissue Eng Part C Methods. 2010 Aug; 16(4):597-607.
  27. Dudley AC, Udagawa T, Melero-Martin JM, Shih SC, Curatolo A, Moses MA, Klagsbrun M. Bone marrow is a reservoir for proangiogenic myelomonocytic cells but not endothelial cells in spontaneous tumors. Blood. 2010 Oct 28; 116(17):3367-71.
  28. Gottlieb D, Kunal T, Emani S, Aikawa E, Brown DW, Powell AJ, Nedder A, Engelmayr GC, Melero-Martin JM, Sacks MS, Mayer JE. In vivo monitoring of function of autologous engineered pulmonary valve. J Thorac Cardiovasc Surg. 2010 Mar; 139(3):723-31.
  29. Melero-Martin JM, Santhalingam S, Al-Rubeai M. Methodology for optimal in vitro cell expansion in tissue engineering. Adv Biochem Eng Biotechnol. 2009; 112:209-29.
  30. Khan ZA, Boscolo E, Picard A, Psutka S, Melero-Martin JM, Bartch TC, Mulliken JB, Bischoff J. Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice. J Clin Invest. 2008 Jul; 118(7):2592-9.
  31. Melero-Martin JM, De Obaldia ME, Kang SY, Khan ZA, Yuan L, Oettgen P, Bischoff J. Engineering robust and functional vascular networks in vivo with human adult and cord blood-derived progenitor cells. Circ Res. 2008 Jul 18; 103(2):194-202.
  32. Melero-Martin JM, Bischoff J. Chapter 13. An in vivo experimental model for postnatal vasculogenesis. Methods Enzymol. 2008; 445:303-29.
  33. Melero-Martin JM, Khan ZA, Picard A, Wu X, Paruchuri S, Bischoff J. In vivo vasculogenic potential of human blood-derived endothelial progenitor cells. Blood. 2007 Jun 1; 109(11):4761-8.
  34. Paruchuri S, Yang JH, Aikawa E, Melero-Martin JM, Khan ZA, Loukogeorgakis S, Schoen FJ, Bischoff J. Human pulmonary valve progenitor cells exhibit endothelial/mesenchymal plasticity in response to vascular endothelial growth factor-A and transforming growth factor-beta2. Circ Res. 2006 Oct 13; 99(8):861-9.
  35. Khan ZA, Melero-Martin JM, Wu X, Paruchuri S, Boscolo E, Mulliken JB, Bischoff J. Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin. Blood. 2006 Aug 1; 108(3):915-21.
  36. Melero-Martin JM, Dowling MA, Smith M, Al-Rubeai M. Expansion of chondroprogenitor cells on macroporous microcarriers as an alternative to conventional monolayer systems. Biomaterials. 2006 May; 27(15):2970-9.
  37. Melero-Martin JM, Dowling MA, Smith M, Al-Rubeai M. Optimal in-vitro expansion of chondroprogenitor cells in monolayer culture. Biotechnol Bioeng. 2006 Feb 20; 93(3):519-33.
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