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.

Researcher Services

Researcher Areas

  • Tissue Engineering
  • Cell Therapy
  • Vascular Biology

Research Departments

Researcher Labs

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Chuang CH, Lin RZ, Melero-Martin JM, Chen YC. Comparison of covalently and physically cross-linked collagen hydrogels on mediating vascular network formation for engineering adipose tissue. Artif Cells Nanomed Biotechnol. 2018 Aug 27; 1-14. View abstract
  2. Nowak-Sliwinska P, Alitalo K, Allen E, Anisimov A, Aplin AC, Auerbach R, Augustin HG, Bates DO, van Beijnum JR, Bender RHF, Bergers G, Bikfalvi A, Bischoff J, Böck BC, Brooks PC, Bussolino F, Cakir B, Carmeliet P, Castranova D, Cimpean AM, Cleaver O, Coukos G, Davis GE, De Palma M, Dimberg A, Dings RPM, Djonov V, Dudley AC, Dufton NP, Fendt SM, Ferrara N, Fruttiger M, Fukumura D, Ghesquière B, Gong Y, Griffin RJ, Harris AL, Hughes CCW, Hultgren NW, Iruela-Arispe ML, Irving M, Jain RK, Kalluri R, Kalucka J, Kerbel RS, Kitajewski J, Klaassen I, Kleinmann HK, Koolwijk P, Kuczynski E, Kwak BR, Marien K, Melero-Martin JM, Munn LL, Nicosia RF, Noel A, Nurro J, Olsson AK, Petrova TV, Pietras K, Pili R, Pollard JW, Post MJ, Quax PHA, Rabinovich GA, Raica M, Randi AM, Ribatti D, Ruegg C, Schlingemann RO, Schulte-Merker S, Smith LEH, Song JW, Stacker SA, Stalin J, Stratman AN, Van de Velde M, van Hinsbergh VWM, Vermeulen PB, Waltenberger J, Weinstein BM, Xin H, Yetkin-Arik B, Yla-Herttuala S, Yoder MC, Griffioen AW. Consensus guidelines for the use and interpretation of angiogenesis assays. Angiogenesis. 2018 May 15. View abstract
  3. Chen J, Fu Y, Day DS, Sun Y, Wang S, Liang X, Gu F, Zhang F, Stevens SM, Zhou P, Li K, Zhang Y, Lin RZ, Smith LEH, Zhang J, Sun K, Melero-Martin JM, Han Z, Park PJ, Zhang B, Pu WT. VEGF amplifies transcription through ETS1 acetylation to enable angiogenesis. Nat Commun. 2017 08 29; 8(1):383. View abstract
  4. Lin RZ, Lee CN, Moreno-Luna R, Neumeyer J, Piekarski B, Zhou P, Moses MA, Sachdev M, Pu WT, Emani S, Melero-Martin JM. Host non-inflammatory neutrophils mediate the engraftment of bioengineered vascular networks. Nat Biomed Eng. 2017; 1. View abstract
  5. Kang KT, Lin RZ, Kuppermann D, Melero-Martin JM, Bischoff J. Endothelial colony forming cells and mesenchymal progenitor cells form blood vessels and increase blood flow in ischemic muscle. Sci Rep. 2017 04 10; 7(1):770. View abstract
  6. Medina RJ, Barber CL, Sabatier F, Dignat-George F, Melero-Martin JM, Khosrotehrani K, Ohneda O, Randi AM, Chan JKY, Yamaguchi T, Van Hinsbergh VWM, Yoder MC, Stitt AW. Endothelial Progenitors: A Consensus Statement on Nomenclature. Stem Cells Transl Med. 2017 May; 6(5):1316-1320. View abstract
  7. Moeinzadeh S, Shariati SRP, Kader S, Melero-Martin JM, Jabbari E. Devitalized Stem Cell Microsheets for Sustainable Release of Osteogenic and Vasculogenic Growth Factors and Regulation of Anti-Inflammatory Immune Response. Adv Biosyst. 2017 Mar; 1(3). View abstract
  8. Barati D, Shariati SRP, 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; 223:126-136. View abstract
  9. 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; 27:151-166. View abstract
  10. 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. View abstract
  11. 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 Oct 22; 5:5200. View abstract
  12. 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. View abstract
  13. 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. View abstract
  14. 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. View abstract
  15. 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. View abstract
  16. 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. View abstract
  17. 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):566-571. View abstract
  18. 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. View abstract
  19. 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. View abstract
  20. 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. View abstract
  21. 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. View abstract
  22. 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. View abstract
  23. 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. View abstract
  24. 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. View abstract
  25. 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. View abstract
  26. Lin RZ, Melero-Martin JM. Bioengineering human microvascular networks in immunodeficient mice. J Vis Exp. 2011 Jul 11; (53):e3065. View abstract
  27. 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. View abstract
  28. Melero-Martin JM, Dudley AC. Concise review: Vascular stem cells and tumor angiogenesis. Stem Cells. 2011 Feb; 29(2):163-8. View abstract
  29. 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. View abstract
  30. 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. View abstract
  31. 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. View abstract
  32. 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. View abstract
  33. 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. View abstract
  34. 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. View abstract
  35. 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. View abstract
  36. 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. View abstract
  37. 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. View abstract
  38. Melero-Martin JM, Bischoff J. Chapter 13. An in vivo experimental model for postnatal vasculogenesis. Methods Enzymol. 2008; 445:303-29. View abstract
  39. 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 01; 109(11):4761-8. View abstract
  40. 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. View abstract
  41. 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 01; 108(3):915-21. View abstract
  42. 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. View abstract
  43. 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. View abstract