9
FROM THE EDITOR Erkin Seker [email protected] A s my first duty as the new Editor of the CEM Communiqué, I would like to thank my predecessor, Dr. Biju Parekkadan, for his work on the newslet- ter and helping with the transition. I also would like to point out that the produc- tion of this newsletter has been a group effort with the instrumental roles of Drs. Basak Uygun and Berk Usta. The last issue focused on viruses, their infection mechanisms, and technol- ogies to detect them. Human body has developed sophisticated ways to evade detrimental effects of viruses. These “bioparticles” can lead to significant phys- iological damage, such as ultimate failure of target organs. Along with viruses, other insults, such as cancer, injury, bacterial in- fections, and autoimmune disorders can destroy organs. These complications have a tremendous impact on the society, pa- tient’s families, and economy. Despite the advances in organ procurement and transport there still exists a large popula- tion of patients who await donor organs and eventually die because of the organ shortfall. Our group has attempted to al- leviate this burden with a multi-pronged approach. Over the years, we have engi- neered bioartificial liver assist devices, as well as stem cell-based therapies, to pro- long the life of patients suffering from liver failure. Recently we have focused on novel tissue engineering approaches to create whole organs. The ability to engi- neer whole organs has been a scientific and medical dream and equally a chal- lenge for a long time. The key obstacles include: (i) maintaining the 3D architec- ture of the organ; (ii) grafting all relevant cell types; (iii) keeping the organ viable; and (iv) minimizing transplant rejection. In this issue, we feature the elegant work performed by Uygun et al. in recon- structing a rat liver. Inspired by the recent advances in engineering of numerous functional organs, such as heart and lung, researchers have successfully removed cells from a rat liver, sparing the struc- tural 3D architecture including the mi- crovasculature intact. They subsequently repopulated this matrix with hepatocytes and showed that the reconstructed liver can sustain its function, that is, albumin and urea secretion, as well as cytochrome P450 expression over 10 days. They final- ly demonstrated that it was possible to transplant the recellularized organs into rats, where the liver tissue maintained its function and morphology for at least 8 hours. This study was published in the prestigious Nature Medicine journal and highlighted in numerous other journals and media sources. Their work constitutes a convincing progress towards whole organ construc- tion. However, more challenges remain. For example, our group has shown that the non-parenchymal cells in the liver (such as fibroblasts, endothelial cells, and Kuppfer cells) play an important role in maintaining the long-term function and viability of hepatocytes. Current efforts are directed towards introducing these cells into the decellularized liver matrices to create an even more realistic synthetic In this issue: Volume 8.1 1. Featured Article: “Liver Reengineering” 2. Recent Publications 3. New To the CEM & Recent Departures 4. Center for Exploration of Mountains 5. Fall 2010 Biomedical Science and Engineering Seminar Series Massachusetts General Hospital 55 Fruit Street GRB 1401 Boston, MA 02114 Tel: 617-371-4882 Fax: 617-371-4951 [email protected] http://cem.sbi.org Layout & Illustration: Don Poulsen [email protected] Previous issues can be found at: http://cem.sbi.org/about-publications.htm

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Page 1: FROM THE EDITOR - The Center for Engineering in Medicinecem.sbi.org/web/communique/communiquev8n1.pdf · 2010-12-01 · neered bioartificial liver assist devices, as well as stem

FROM THE EDITOR Erkin Seker [email protected]

As my first duty as the new Editor of the CEM Communiqué, I would like to thank my predecessor, Dr. Biju

Parekkadan, for his work on the newslet-ter and helping with the transition. I also would like to point out that the produc-tion of this newsletter has been a group effort with the instrumental roles of Drs. Basak Uygun and Berk Usta.

The last issue focused on viruses, their infection mechanisms, and technol-ogies to detect them. Human body has developed sophisticated ways to evade detrimental effects of viruses. These “bioparticles” can lead to significant phys-iological damage, such as ultimate failure of target organs. Along with viruses, other insults, such as cancer, injury, bacterial in-fections, and autoimmune disorders can destroy organs. These complications have a tremendous impact on the society, pa-tient’s families, and economy. Despite the advances in organ procurement and transport there still exists a large popula-tion of patients who await donor organs and eventually die because of the organ shortfall. Our group has attempted to al-leviate this burden with a multi-pronged approach. Over the years, we have engi-neered bioartificial liver assist devices, as well as stem cell-based therapies, to pro-long the life of patients suffering from liver failure. Recently we have focused on novel tissue engineering approaches to create whole organs. The ability to engi-

neer whole organs has been a scientific and medical dream and equally a chal-lenge for a long time. The key obstacles include: (i) maintaining the 3D architec-ture of the organ; (ii) grafting all relevant cell types; (iii) keeping the organ viable; and (iv) minimizing transplant rejection.

In this issue, we feature the elegant work performed by Uygun et al. in recon-structing a rat liver. Inspired by the recent advances in engineering of numerous functional organs, such as heart and lung, researchers have successfully removed cells from a rat liver, sparing the struc-tural 3D architecture including the mi-crovasculature intact. They subsequently repopulated this matrix with hepatocytes and showed that the reconstructed liver can sustain its function, that is, albumin and urea secretion, as well as cytochrome P450 expression over 10 days. They final-ly demonstrated that it was possible to transplant the recellularized organs into rats, where the liver tissue maintained its function and morphology for at least 8 hours. This study was published in the prestigious Nature Medicine journal and highlighted in numerous other journals and media sources.

Their work constitutes a convincing progress towards whole organ construc-tion. However, more challenges remain. For example, our group has shown that the non-parenchymal cells in the liver (such as fibroblasts, endothelial cells, and Kuppfer cells) play an important role in maintaining the long-term function and viability of hepatocytes. Current efforts are directed towards introducing these cells into the decellularized liver matrices to create an even more realistic synthetic

In this issue:Volume 8.11. Featured Article: “Liver Reengineering”

2. Recent Publications

3. New To the CEM & Recent Departures

4. Center for Exploration of Mountains

5. Fall 2010 Biomedical Science and Engineering Seminar Series

Massachusetts General Hospital

55 Fruit Street GRB 1401

Boston, MA 02114

Tel: 617-371-4882 Fax: 617-371-4951

[email protected] http://cem.sbi.org

Layout & Illustration: Don Poulsen [email protected]

Previous issues can be found at: http://cem.sbi.org/about-publications.htm

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CEM Communique

Volume 8.1liver. If successful, this technology can save thousands of lives every year.

There have been numerous high-impact publica-tions from other members of the CEM, including devel-opment of novel techniques to capture and identify cir-culating tumor cells (Stott et al., Sci Transl Med, 2010 and Stott et al., PNAS, 2010) and engineering microfluidic platforms to study neutrophil genomics and proteomics (Kotz et al., Nat Med, 2010).

Since the last issue, there have been a large num-ber of new researchers joining our laboratory. Here we formally welcome all and look forward to seeing the exciting ideas and skills that they will contribute to our laboratory.

LIVER REENGINEERINGBasak Uygun

Liver disease is the 12th leading cause of death registering roughly 27,000 deaths annually in the United States. The only definitive treatment meth-

od for end stage liver failure is orthotopic transplanta-tion and there are about 16,000 people waiting for a suitable donor organ (Organ Procurement and Trans-plantation Network, http://www.optn.org/). There are approximately 10,000 new additions made to the wait-ing list each year. Unfortunately, the number of trans-plantations performed (~6,000 annually) is limited by the number of healthy donor livers. The shortage arises because majority of donor organs are rejected due to large ischemic times, or are of poor health with condi-tions like steatosis. Considering the high prevalence of hepatitis C (~3%), the demand will increase significantly in the next decade [1]. Hence, there is an urgent need for practicable therapies for liver failure.

Cell transplantation offers a less invasive alter-native to liver transplantation and years of laboratory studies and experience in small number of human sub-jects has demonstrated its efficacy [2-5]. However, cell transplantation for liver diseases has shown long-term functional limitations due to lack of engraftment [2, 4, 6-9], and is noted to be 10% or lower . Tissue engineer-ing offers the tools to build tissues from grounds up and thus far, the approach has been able to partially improve cell engraftment in animal models by enhancing cell-cell contact and providing non-immunogenic matrices prior to transplantation [10]. One of the main challenges

of tissue engineered constructs for liver is the delivery of oxygen and other nutrients to the highly metaboli-cally active liver cells (hepatocytes) incorporated into the construct. So far, traditional tissue engineering ap-proach using synthetic biomaterials and scaffold fab-rication techniques has been limited to creation liver tissues that have been transplanted into highly vascu-larized regions in the body such as subcutaneous [11, 12], intra-abdominal [13] or even over the spleen [14]. A functional liver graft that can readily be connected to the recipient’s blood stream is yet to be developed.

Preparation of natural materials through tissue decellularization for tissue engineering applications has long attracted attention. The technique involves wash-ing of the tissue with detergents to remove the cells by application of some kind of mechanical force, e.g. agita-tion, and the resulting material is the extracellular matrix with the composition specific to the tissue. The decel-lularized ECM potentially retains the architecture of the original tissue including the functional aspects of the native microvasculature [15]. The potential applications of decellularized matrix in tissue engineering has been demonstrated for a number of tissues including bladder [16], artery [17], esophagus [18], skin [19], trachea [20]. More recently, the Taylor group reported the decellular-ization of an entire heart through perfusion, preserving the original architecture and original microvascular net-work allowing for extensive recellularization [21].

Figure 1 - Whole organ scaffolds prepared via perfusion decellular-ization (a) Images of liver throughout the decellualrization process (b) vascular architecture of the liver scaffold compared to normal liver, blue venous red portal structure (c),(d) electron micrograph images show that both large and small vessels are preserved in the decellularized liver matrix.

In a report recently published in Nature Medicine, we have used perfusion decellularization to prepare whole liver grafts, and introduced perfusion seeding and culture techniques for the preparation of recellular-ized liver grafts for transplantation. We used ischemic

2

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Volume 8.1livers procured from rats and perfused them with a se-ries of sodium dodecyl sulfate (SDS) solutions (0.01% SDS for 24 h, with 0.1% SDS for 24 h and with 1% SDS for 24 h) through the portal vein. This procedure yield-ed a fully decellularized construct that stained positive for the ECM proteins histologically similar to native liver (Fig. 1a). We found that 100% of the fibrillar collagen and approximately 50% of the glycosaminoglycans of native liver were retained following decellularization. Residual DNA content in the DLM was less than 3%. The decel-lularized scaffolds also retain their vascular structure as confirmed via corrosion casting through the portal vein (Fig. 1b) and scanning electron microscopy (Fig. 1c).

Figure 2 - Recellularization of the decellularized liver matrix. (a) Set-up for the perfusion culture of recellularized grafts (b) Histology and immunohistochemistry of the recellularized grafts (c) Hepatic function of the recellularized grafts during in vitro culture. Scale bars 100 µm.

The decellularized liver matrix was repopulated with up to 200×106 adult primary hepatocytes via per-fusion and cultured under perfusion with oxygenated medium for up to 10 days (Fig. 2a). The seeding efficien-cy was 95.6 ± 3.4%. The grafts remained viable during the culture; the number of TUNEL positive cells didn’t increase significantly during the first 2 days of culture and the extracellular lactate dehydrogenase levels dur-ing perfusion were identical to those obtained with pri-mary cultures of hepatocytes, indicating no significant damage to cells in decellularized liver matrix under con-tinuous circulation of cell culture medium. In addition, hepatocytes demonstrated the ability to engraft in the liver matrix and around the vessels.

As judged H&E staining (Fig. 2b), the cells were well distributed and healthy after 2 days and they were positive for functional markers such as albumin, glucose 6-phosphatase and UGT1A. There was steady produc-tion of albumin, urea, and total bile acids proving he-patic functionality in the recellularized liver (Fig. 2c). Al-bumin production rate by the recellularized liver graft was about 30% of normal adult rat liver [22].

Analysis of the expression of drug metabolism enzymes via quantitative RT-PCR at 2 d revealed that ex-pression levels of Phase I and Phase II drug metabolism enzymes in the recellularized liver were similar to those measured in sandwich hepatocyte cultures (p-value 0.0499). Ultimately reconstruction of liver grafts in vi-tro requires the addition of non-parenchymal cells. As a preliminary test, seeding of a non-parenchymal compo-nent to the recellularized liver graft was demonstrated by incorporating microvascular endothelial cells (ECs) to the hepatocyte repopulated graft, and testing by per-fusion-culture for up to 5 d to allow for EC engraftment. Histological analysis showed that endothelial cells were capable of lining the vasculature encircled by hepato-cytes at 3 d of culture.

Figure 3 - Evaluation of the in vivo performance of the recellularized grafts (a) Heterotopic transplantation of the grafts (b) Urea and al-bumin secretion by the recellularized graft during ex vivo blood

perfusion. Scale bars 10 mm.

Availability of functional vascular structure offer the opportunity to transplant the recellularized liver graft by connecting the graft to the blood supply, al-

3

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CEM Communique

Volume 8.1lowing for the transplantation of a critical hepatocyte mass while avoiding ischemic damage due to poor graft perfusion. Briefly, recipient animals underwent unilat-eral nephrectomy to prepare a viable site for auxiliary liver graft transplantation. The renal vein and artery were used to as ports to create blood flow within the graft. Upon unclamping of the artery, the graft was per-fused, quickly filling with blood, and appropriate efflux was established within 5 min (Fig 3a). The recellular-ized graft was kept in vivo for 8 h prior to harvesting for further analysis. TUNEL staining revealed that there was minimal damage to the hepatocytes due to the ar-terial blood flow and consequent shear stress during 8 h of transplantation. The functional performance of the recellularized grafts was evaluated in an ex vivo blood perfusion model adopted as a surrogate for transplanta-tion. Over 24 h of perfusion, the grafts remained viable and functional as displayed by production of albumin and urea (Fig 3b).

Our work demonstrates the decellularization of ischemic rat livers by portal vein perfusion and its char-acterization for the first time. We show the preserva-tion of both structural and basement membrane-based components of the native liver extracellular matrix, as well as the retention of a functional microvascular net-work. Decellularized liver matrix supported the engraft-ment and in vitro metabolic function of up to 200×106 hepatocytes with over 90% engraftment efficiency. Retention of vascular structures allowed for transplan-tation of recellularized liver graft in rats and post-trans-plantation analysis demonstrated preservation of hepa-tocyte structure and function with minimal indications of ischemic damage. Preliminary recellularization with endothelial cells also indicates attachment and viabil-ity within the recellularized matrix in vitro. Overall, the methods and techniques developed in this study pres-ent the first step towards manufacture of auxiliary liver grafts as an alternative source of organs for liver trans-plantation.

References1. Guidotti, L.G. and F.V. Chisari, Immunobiology and Pathogenesis of Viral Hepati-tis. Annual Review of Pathology: Mechanisms of Disease, 2006. 1: p. 23–61.

2. Horslen, S.P., et al., Isolated hepatocyte transplantation in an infant with a se-vere urea cycle disorder. Pediatrics, 2003. 111(6 Pt 1): p. 1262-7.

3. Fox, I.J., et al., Treatment of the Crigler-Najjar syndrome type I with hepatocyte transplantation. N Engl J Med, 1998. 338(20): p. 1422-6.

4. Fisher, R.A. and S.C. Strom, Human hepatocyte transplantation: worldwide re-sults. Transplantation, 2006. 82(4): p. 441-9.

5. Chen, Y., et al., Transplantation of human hepatocytes cultured with deleted variant of hepatocyte growth factor prolongs the survival of mice with acute liver failure. Transplantation, 2005. 79(10): p. 1378-85.

6. Ringers, J., et al., Reuse of auxiliary liver grafts in second recipients with chronic liver disease. Am J Transplant, 2007. 7(11): p. 2615-8.

7. Dhawan, A., et al., Hepatocyte transplantation for inherited factor VII deficiency. Transplantation, 2004. 78(12): p. 1812-4.

8. Fisher, R.A., et al., Optimization of conditions for clinical human hepatocyte in-fusion. Cell Transplant, 2004. 13(6): p. 677-89.

9. Puppi, J., et al., Hepatocyte transplantation followed by auxiliary liver transplan-tation--a novel treatment for ornithine transcarbamylase deficiency. Am J Trans-plant, 2008. 8(2): p. 452-7.

10. Langer, R. and J.P. Vacanti, Tissue engineering. Science, 1993. 260(5110): p. 920-6.

11. Ohashi, K., et al., Engineering functional two- and three-dimensional liver sys-tems in vivo using hepatic tissue sheets. Nat Med, 2007. 13(7): p. 880-5.

12. Soto-Gutierrez, A., et al., Reversal of mouse hepatic failure using an implanted liver-assist device containing ES cell-derived hepatocytes. Nat Biotechnol, 2006. 24(11): p. 1412-9.

13. Demetriou, A.A., et al., Replacement of liver function in rats by transplantation of microcarrier-attached hepatocytes. Science, 1986. 233(4769): p. 1190-2.

14. Soto-Gutierrez, A., et al., Construction and transplantation of an engineered hepatic tissue using a polyaminourethane-coated nonwoven polytetrafluoroeth-ylene fabric. Transplantation, 2007. 83(2): p. 129-37.

15. Badylak, S.F., The extracellular matrix as a biologic scaffold material. Biomateri-als, 2007. 28(25): p. 3587-93.

16. Yoo, J.J., et al., Bladder augmentation using allogenic bladder submucosa seeded with cells. Urology, 1998. 51(2): p. 221-5.

17. Dahl, S.L., et al., Decellularized native and engineered arterial scaffolds for transplantation. Cell Transplant, 2003. 12(6): p. 659-66.

18. Nieponice, A., T.W. Gilbert, and S.F. Badylak, Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model. Annals of Thoracic Surgery, 2006. 82(6): p. 2050-2058.

19. Schechner, J.S., et al., Engraftment of a vascularized human skin equivalent. Faseb J, 2003. 17(15): p. 2250-6.

20. Macchiarini, P., et al., Clinical transplantation of a tissue-engineered airway. Lancet, 2008. 372(9655): p. 2023-30.

21. Ott, H.C., et al., Perfusion-decellularized matrix: using nature’s platform to en-gineer a bioartificial heart. Nat Med, 2008. 14(2): p. 213-221.

22. Hoffenberg, R., Measurement of the synthesis of liver-produced plasma pro-teins with particular reference to dietary protein and amino acid supply. Biochem J, 1972. 129(2): p. 3P.

RECENT PUBLICATIONS 1. Jiao, J., et al., A mesenchymal stem cell potency assay. Methods Mol Biol, 2011. 677: p. 221-31.

2. Yagi, H., et al., Mesenchymal stem cells: mechanisms of immu-nomodulation and homing. Cell Transplant, 2010. 19(6): p. 667-79.

3. Yagi, H., et al., Reactive bone marrow stromal cells attenuate sys-temic inflammation via sTNFR1. Mol Ther, 2010. 18(10): p. 1857-64.

4. Yagi, H., et al., Bone marrow mesenchymal stromal cells attenu-ate organ injury induced by LPS and burn. Cell Transplant, 2010. 19(6): p. 823-30.

4

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CEM Communique

Volume 8.15. Wolfer, A., et al., MYC regulation of a “poor-prognosis” metastatic cancer cell state. Proc Natl Acad Sci U S A, 2010. 107(8): p. 3698-703.

6. van Poll, D., et al., Human immune reactivity against liver sinu-soidal endothelial cells from GalTalpha(1,3)GalT-deficient pigs. Cell Transplant, 2010. 19(6): p. 783-9.

7. Uygun, K., et al., Diluted blood reperfusion as a model for trans-plantation of ischemic rat livers: alanine aminotransferase is a di-rect indicator of viability. Transplant Proc, 2010. 42(7): p. 2463-7.

8. Uygun, B.E., et al., Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med, 2010. 16(7): p. 814-20.

9. Stott, S.L., et al., Isolation and characterization of circulating tu-mor cells from patients with localized and metastatic prostate can-cer. Sci Transl Med, 2010. 2(25): p. 25ra23.

10. Stott, S.L., et al., Isolation of circulating tumor cells using a mi-crovortex-generating herringbone-chip. Proc Natl Acad Sci U S A, 2010.

11. Soto-Gutierrez, A., et al., Cell delivery: from cell transplantation to organ engineering. Cell Transplant, 2010. 19(6): p. 655-65.

12. Sharma, N.S., D. Nagrath, and M.L. Yarmush, Adipocyte-derived basement membrane extract with biological activity: applications in hepatocyte functional augmentation in vitro. FASEB J, 2010. 24(7): p. 2364-74.

13. Seker, E., et al., The fabrication of low-impedance nanoporous gold multiple-electrode arrays for neural electrophysiology stud-ies. Nanotechnology, 2010. 21(12): p. 125504.

14. Parekkadan, B., et al., Bone Marrow Stromal Cell Transplants Prevent Experimental Enterocolitis and Require Host CD11b+ Sple-nocytes. Gastroenterology, 2010.

15. Oakey, J., et al., Particle focusing in staged inertial microfluidic devices for flow cytometry. Anal Chem, 2010. 82(9): p. 3862-7.

16. Lee, H.J., et al., Ultra-rapid vitrification of mouse oocytes in low cryoprotectant concentrations. Reprod Biomed Online, 2010. 20(2): p. 201-8.

17. Kotz, K.T., et al., Clinical microfluidics for neutrophil genomics and proteomics. Nat Med, 2010. 16(9): p. 1042-7.

18. Konry, T., et al., Droplet-based microfluidic platforms for single T cell secretion analysis of IL-10 cytokine. Biosens Bioelectron, 2010.

19. Jindal, R., S.J. Patel, and M.L. Yarmush, Tissue-Engineered Mod-el for Real-Time Monitoring of Liver Inflammation. Tissue Eng Part C Methods, 2010.

20. Irimia, D., Microfluidic technologies for temporal perturbations of chemotaxis. Annu Rev Biomed Eng, 2010. 12: p. 259-84.

21. Cho, C.H., et al., Layered patterning of hepatocytes in co-cul-ture systems using microfabricated stencils. Biotechniques, 2010.

48(1): p. 47-52.

22. Chen, G.D., et al., Concentration and purification of human im-munodeficiency virus type 1 virions by microfluidic separation of superparamagnetic nanoparticles. Anal Chem, 2010. 82(2): p. 723-8.

23. Chen, C., et al., Microfluidic isolation and transcriptome analysis of serum microvesicles. Lab Chip, 2010. 10(4): p. 505-11.

24. Butler, K.L., et al., Burn injury reduces neutrophil directional migration speed in microfluidic devices. PLoS One, 2010. 5(7): p. e11921.

25. Ambravaneswaran, V., et al., Directional decisions during neu-trophil chemotaxis inside bifurcating channels. Integr Biol (Camb), 2010.

26. Yagi, H., et al., Long-term superior performance of a stem cell/hepatocyte device for the treatment of acute liver failure. Tissue Eng Part A, 2009. 15(11): p. 3377-88.

27. Stoothoff, W., et al., Differential effect of three-repeat and four-repeat tau on mitochondrial axonal transport. J Neurochem, 2009. 111(2): p. 417-27.

28. Soto-Gutierrez, A., et al., Stem cells for liver repopulation. Curr Opin Organ Transplant, 2009. 14(6): p. 667-73.

29. Roach, K.L., et al., High throughput single cell bioinformatics. Biotechnol Prog, 2009. 25(6): p. 1772-9.

30. Kidambi, S., et al., Oxygen-mediated enhancement of primary hepatocyte metabolism, functional polarization, gene expres-sion, and drug clearance. Proc Natl Acad Sci U S A, 2009. 106(37): p. 15714-9.

31. Izamis, M.L., et al., Effects of burn injury on markers of hyperme-tabolism in rats. J Burn Care Res, 2009. 30(6): p. 993-1001.

32. Irimia, D. and M. Toner, Spontaneous migration of cancer cells under conditions of mechanical confinement. Integr Biol (Camb), 2009. 1(8-9): p. 506-12.

33. Irimia, D., Cutting edge: electronic counting of white blood cells. Lab Chip, 2009. 9(20): p. 2875-6.

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CEM Communique

Volume 8.1

NEW MEMBER PROFILE Fangjing Wang

Fangjing joined the Therapeutics and Applied Immunology Group at the CEM in May 2010. He received his PhD in Biomedical Engineering from Case Western Reserve University where he focused on biomedical imaging of stem cells using bioluminescence (BLI) and positron emission tomography (PET) in the treatment of graft-versus-host disease (GVHD).

Fangjing is excited about the multidisciplinary & dynamic research environment at the CEM. His work will involve stem cell therapy, biomedical imaging and mathematical modeling. The ultimate goal is to understand and improve stem cell based therapies in the treatment of various diseases. In his free time, Fangjing plays table-tennis with his friends.

Sinem Perk

Sinem Perk joined the Metabolism, Transplantation & Tissue Engineering Group at the CEM in September 2010. Sinem received her Ph.D. in Chemical Engineering at Illinois Institute of Technology where she studied the supervision and control of complex distributed processes with agent-based systems. Her research at the CEM is currently focused on the metabolic modeling of hepatic hypermetabolism and ischemic injury for the purpose of developing methodologies to alleviate hyperme-tabolism, or to improve the organ viability for transplantation. In her free time, Sinem enjoys reading, cooking and traveling.

6

Molecular and Cellular Bioengineering Dhruv Sarin Worcester Polytechnic Institute

Shan Gao, PhD Chem Eng, Columbia U

Beili Zhu, PhD Biomed Eng, U Texas

Abhinav Bhushan, PhD Mech Eng, Louisiana State U

Shyam Bale, PhD Chem&Bio Eng, RPI

Monica Casali, PhD Polymer Sci, Politecnico di Milano

Suraj Patel, PhD Biomed Eng, MIT

Therapeutics and Applied ImmunologyMatt Li Bioeng, UCSD

Jungwoo Lee, PhD BIomed Eng, U Michigan

Fangjing Wang, PhD Biomed Eng, Case Western Reserve U

Keyue Shen, PhD Biomed Eng, Columbia U

Mohamed Hammad, PhD Pharmacol, U Mississippi

Arvin Iracheta-Vellve Biology, Boston College

NEW TO THE CEMMetabolism, Transplant & Tissue EngineeringBerk Usta, PhD Chem Eng, U Florida

Ming Chen, PhD BIomed Eng, U Massachusetts

Aaron Rosado, PhD Chem&Bio Eng, MIT

Nima Saeidi, PhD Mech Eng, Northeastern U

Gavi Price, PhD Biomed Eng, Boston U

Tim Berendsen, MD Surgery, University of Utrecht

Shahram Bheshad Chem&Bio Eng, SUNY Buffalo

Qiang Liu, MD,PhD Transpl Surg, University Leuven

Sinem Perk, PhD Chem Eng, Illinois Inst Tech

BioMEMS Resource CenterMarta-Fernandez Suarez, PhD Chemistry, MIT

Ian Y. Wong, PhD Mat Sci & Eng, Stanford U

A. J. Aranyosi, PhD HST, MIT

George Korir Biomed Eng, Johns Hopkins U

Fred Floyd Mech Eng, Villanova U

Melissa Yu Olin College

Ted de Groot Cornell U

Bryan Hassell Mech Eng, Villanova U

Hansang Cho, PhD UC Berkeley

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Volume 8.1

Molecular and Cellular Bioengineering Dhruv Sarin Worcester Polytechnic Institute

Shan Gao, PhD Chem Eng, Columbia U

Beili Zhu, PhD Biomed Eng, U Texas

Abhinav Bhushan, PhD Mech Eng, Louisiana State U

Shyam Bale, PhD Chem&Bio Eng, RPI

Monica Casali, PhD Polymer Sci, Politecnico di Milano

Suraj Patel, PhD Biomed Eng, MIT

Therapeutics and Applied ImmunologyMatt Li Bioeng, UCSD

Jungwoo Lee, PhD BIomed Eng, U Michigan

Fangjing Wang, PhD Biomed Eng, Case Western Reserve U

Keyue Shen, PhD Biomed Eng, Columbia U

Mohamed Hammad, PhD Pharmacol, U Mississippi

Arvin Iracheta-Vellve Biology, Boston College

7

RECENT DEPARTURES FROM CEM Dino DiCarlo Assistant Professor, UCLA

Jon Edd Assistant Professor, Vanderbilt U

Alessandra Moore Student, UMass Medical School

Dina Tsukrov Student, Albert Einstein College of Medicine

Chey Collura Student, St George’s U Medical School

Chihchen Chen Scientific Advisory Board, Daktari Diagnostics Inc., Cambridge, MA

Chia Hsien Hsu Assistant Investigator, National Health Research Institute, Taiwan

Sunitha Nagrath Assistant Professor, Chemical Eng, U Michigan and Visiting Professor at MGH

John Oakey Assistant Professor, Chemical Engineering, University of Wyoming

Amit Gupta SVTC Technologies in San Jose, CA

Carley Shulman Technician, Emory U

Deepak Nagrath Assistant Professor, Chemical & Biomolecular Engineering, Rice U

Sri Kidambi Assistant Professor, Chemical and Biomolecular Engineering, U Nebraska

Marco Avila Associate, McKinsey and Company, Chile

Yoni Goldwasser Research Scientist, Teva Pharmaceuticals

Piyush Koria Assistant Professor, Chemical & Biomedical Engineering, U South Florida

Eric Yang Research Engineer, Bioinformatics, Johnson & Johnson

Candice Calhoun Student, Physician’s Assistant Program, Duke U

Eugene Berdichevsky Research Associate, Neurology, MGH

Hiroshi Yagi Assistant Professor, Surgery, Keio U School of Medicine, Japan

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CEM Communique

Volume 8.1

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Going away party for Hiro

Boston Hub on Wheels 2010 @ Jacob Wirth

SOCIAL EVENTS at CEM

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CEM Communique

Volume 8.1

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Biomedical Science & EngineeringFall 2010 Seminar

September 10Tillman Gerngross, PhDBiomedical Engineering, Dartmouth CollegeRecent Advances in Yeast Biotechnology

October 22Joan S. Brugge, PhDCell Biology, Harvard Medical SchoolEngineering Cell Culture Models to Study Morphogenesis and Oncogenesis

November 5Kyongbum Lee, PhDTufts UEngineering Lean Fat Tissue

November 12Nick Melosh, PhDStanford UEngineering Cell Access with Nano-functionalized Posts

November 19William Shih, PhDHarvard USelf-assembly of DNA into Nanoscale Three-dimensional Shapes

December 3Hongbo Luo, PhDHarvard Medical SchoolSmall-molecule screen identifies Reactive Oxygen Species as key regulators of neutrophil chemotaxis