The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases

 Radbod Darabi, M.D, Ph.D.

Radbod Darabi, M.D, Ph.D.

Assistant Professor, Center for Stem Cell and Regenerative Medicine

Radbod.Darabi@uth.tmc.edu

713-500-3411

“Using Stem Cells for Skeletal Muscle Repair”

Dr. Darabi’s lab main interest is using pluripotent stem cells for skeletal muscle regeneration in muscular dystrophies and muscle injuries. During the last few years, Dr. Darabi has developed novel methods for using mouse/ human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells) for cell therapy in mice models of muscular dystrophies.

Here at CSCRM/IMM, his research team works on directed differentiation of human ES/iPS cells toward skeletal myogenic progenitors using knock-in reporters, improving stem cell delivery and engraftment using intra-arterial cell delivery, studying mechanisms involved in cell homing into the muscle after systemic cell delivery, as well as iPS disease modeling and gene editing technologies for gene correction in muscular dystrophies.

His lab is currently funded by a NIH/RO-1 grant to study myogenic differentiation of human ES/iPS cells and in vivo stem cell based therapy in mice models of muscle disorders.

Ongoing Research Projects

    1. Directed differentiation of human ES/iPS cells toward myogenic progenitors using knock-in reporters
    2. iPS cell disease modeling and CRISPR/Cas9 mediated gene correction
    3. Systemic (intra-arterial) stem cell delivery approach for cell therapy in muscular dystrophies
    4. Using bio-scaffolds/stem cells for skeletal muscle injury repair

             

            Selected Publications

              1. Wu J, Hunt SD, Xue H, Liu Y, Darabi R. Generation and Validation of PAX7 Reporter Lines from Human iPS Cells Using CRISPR/Cas9 Technology. Stem Cell Research. 2016 Jan 13;16(2):220-228.
              2. Wu J, Hunt SD, Xue H, Liu Y, Darabi R. Generation and Characterization of a MYF5 Reporter Human iPS Cell Line Using CRISPR/Cas9 Mediated Homologous Recombination. Scientific Reports. 2016 Jan 5;6:18759. doi: 10.1038/srep18759.
              3. Matthias N, Hunt SD, Wu J, Darabi R. Skeletal muscle perfusion and stem cell delivery in muscle disorders using intra-femoral artery canulation in mice. Experimental Cell Research. 2015 Nov 15;339(1):103-11.
              4. Darabi R, Perlingeiro RC. Derivation of Skeletal Myogenic Precursors from Human Pluripotent Stem Cells Using Conditional Expression of PAX7. Methods in Molecular Biology. 2014 Nov 18.
              5. Skoglund G, Lainé J, Darabi R, Fournier E, Perlingeiro R, Tabti N. Physiological and ultrastructural features of human induced pluripotent and embryonic stem cell-derived skeletal myocytes in vitro. Proceedings of the National Academy of Sciences USA (PNAS). 2014 Jun 3;111(22):8275-80.
              6. Arpke RW, Darabi R, Mader TL, Zhang Y, Toyama A, Lonetree CL, Nash N, Lowe DA, Perlingeiro RC, Kyba M. A New Immuno- Dystrophin-Deficient Model, the NSG-Mdx4cv Mouse, Provides Evidence for Functional Improvement Following Allogeneic Satellite Cell Transplantation. Stem Cells, 2013 Aug; 31(8):1611-20.
              7. Filareto A, Parker S, Darabi R, Borges L, Iacovino M, Schaaf T, Mayerhofer T, Chamberlain J, Ervasti J, Scott McIvor R, Kyba M, Perlingeiro RCR. An ex vivo Gene Therapy Approach to Treat Muscular Dystrophy Using iPS cells. Nature Communications. 2013; 4:1549.
              8. Darabi R, Arpke RW, Irion S, Dimos JT, Grskovic M, Kyba M, Perlingeiro RC. Human ES and iPS-Derived Myogenic Progenitors Restore Dystrophin and Improve Contractility upon Transplantation in Dystrophic Mice. Cell Stem Cell, 2012 May; 10 (5), 610-619.
              9. Darabi R, Santos FN, Filareto A, Pan W, Koene R, Rudnicki MA, Kyba M, Perlingeiro RC. Assessment of the myogenic stem cell compartment following transplantation of pax3/pax7-induced embryonic stem cell-derived progenitors. Stem Cells, 2011 May; 29(5):777-90.
              10. Ramos AL, Darabi R (equal contribution), Akbarloo N, Borges L, Catanese J, Dineen SP, Brekken RA, Perlingeiro RC. Clonal Analysis Reveals a Common Progenitor for Endothelial, Myeloid, and Lymphoid Precursors in Umbilical Cord Blood. Circulation Research, 2010 Dec 10; 107(12):1460-9.
              11. Darabi R, Baik J, Clee M, Kyba M, Tupler R, Perlingeiro RC. Engraftment of embryonic stem cell- derived myogenic progenitors in a dominant model of muscular dystrophy. Experimental Neurology, 2009 Nov; 220(1):212-6.
              12. Darabi R, Gehlbach K, Bachoo MR, Kamath S, Osawa M, Kam KE, Kyba M, Perlingeiro RC. Functional skeletal muscle regeneration from differentiating embryonic stem cells. Nature medicine, 2008; 14 (2): 134-143.

                       

                         Pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/?term=darabi+r

              darabiFIG1final2016

              Generation of a double reporter human iPS cell for PAX7 and MYF5 using a CRISPR/Cas9 mediated homologous recombination

              (A) Targeting strategy using a bicistronic reporter system

              (B) GFP TdTomato reporter activity following cell differentiation and gene activation

              darabiFIG2final2016

              Intra-femoral artery stem cell delivery into mdx mouse hindlimb muscle to restore dystrophin

              (A) Isolation of femoral artery from nerve and vein and canulation using a catheter to perfuse the hindlimb

              (B) NIRF imaging of the perfused muscle to validate proper perfusion and engraftment of human stem cell into muscle expressing dystrophin

              darabiFIG3final2016

              Using bio-scaffold seeded with stem cells to repair muscle mass loss injury

              (A) A hydrogel seeded with LacZ labeled stem cells demonstrates proper cell survival within the scaffold

              (B) A severe muscle mass loss injury with massive fibrosis (left) is repaired using bio-scaffold/stem cell transplantation. LacZ positive donor derived fibers replace the fibrosis one month after transplantation