Research Interests

Principal Investigator(s): Paul Gores, M.D. and Craig Halberstadt, Ph.D.

Agency: Sertoli Technologies, Inc., Juvenile Diabetes Foundation International, and Health Services Foundation

Type: Research Contract, Period: January, 1997 to 2003 and 2004 -2005

This is a sponsored research project based on early observations that Sertoli cells isolated from the testis will establish a local immunoprotective barrier for allogeneic pancreatic islets in a diabetic rodent model.  The specific aims of this project are to: 1) Develop a reproducible Sertoli cell isolation process; 2) Develop in vitro and in vivo characterization assays and identify specific markers for eventual quality control tests; 3) Identify a clinically relevant site in both a small and large animal model; 4) Develop a biomaterial construct in order to co-localize the Sertoli cells and the islets; 5) Develop a transplantation strategy for a allogeneic pre-clinical model; 6) Perform parallel experiments with porcine tissue; and 7) Transfer this technology to further product development and clinical trials.  This is a multi-disciplinary project that is being jointly developed by our laboratory and Drs. Ray Rajotte and Greg Korbutt at the University of Alberta and is in the early stages of development.

“Characterization of Sertoli Cell and Pancreatic Islet Transplants” (Characterizing the Sertoli Cells for in vitro and in vivo identification using immunohistochemisty, confocal microscopy and in situ hybridization techniques)

Professional Experience

Current Positions:

• Senior Research Scientist, Director of Tissue Engineering; Carolinas Medical Center; Charlotte, North Carolina

• Adjunct Assistant Professor, Biology Department, University of North Carolina at Charlotte

• Adjunct Associate Professor, Greenville Hospital System / Clemson University Biomedical Cooperative

Previous Positions:

• 1985 to 1991 Graduate Student Research Assistant, Department of Chemical Engineering & the Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan

• 1986 to 1989 Consultant, BioQuant, Inc, Ann Arbor, Michigan

• 1991 to 1994 Manager of Bioprocess Research, Advanced Tissue Sciences, La Jolla, California

• 1994 Director of Product Development, Advanced Tissue Sciences, La Jolla, California

• 1994 to 1996 Director of Tissue Engineering, Desmos, Inc., San Diego, California

• 1996 to Present Senior Research Scientist, Director of Tissue Engineering, Department of General Surgery, Carolinas Medical Center, Cannon Research Institute, Charlotte, North Carolina

Awards and Other Professional Activities

• 1987 to 1988          Rackham Research Partner Fellowship - University of Michigan

• 1997 to 2000          Chairman of the Hybrid Artificial Organs Special Interest Group, Society of Biomaterials

• 1997 to 2000          Scientific Advisory Board Member - Reprogenesis, Inc.

• 1997 to 2003          Scientific Advisory Board Member - Sertoli Technologies, Inc.

Education

• University of Michigan, Ann Arbor, Michigan, B.S., Microbiology, 1983

• University of Michigan, Ann Arbor, Michigan, M.S., Bioengineering, 1986

• University of Michigan, Ann Arbor, Michigan, Ph.D., Bioengineering, 1991

Selected Publications

1)       Halberstadt, C.R., Williams, D., Emerich, D., Goddard, M., Vasconcellos, A.V., Curry, W., Bhatia, A., and P.F. Gores. Subcutaneous Transplantation of Islets into Streptozocin-induced Diabetic Rats. Cell Transplantation. Accepted.

2)       Halberstadt, C.R., Emerich, D.F., and P. Gores. Use of Sertoli cell transplants to provide local immunoprotection for tissue grafts. Expert Opinion on Biological Therapy, June; 4(6):813-825, 2004.

3)       Rasley, A., Marriott, I., Halberstadt, C.R., Bost, K.L., and J. Anguita. Substance P augments Borrelia burgdorferi induced Prostaglandin E(2) production by murine microglia. Journal of Immunology May 1; 172(9):5707-13, 2004.

4)       Dufour, J.M., Gores, P., Hemendinger, R., Emerich, D.F., and C.R. Halberstadt. Transgenic Sertoli cells as a vehicle for gene therapy. Cell Transplantation 13(1):1-6, 2004.

5)       Dufour, J.M. Hemendinger, R., Halberstadt, C.R., Gores, P., Emerich, D.F., Korbutt, G.S. and R.V. Rajotte. Genetically Engineered Sertoli Cells Are Able To Survive Allogeneic Transplantation. Gene Therapy 11(8):694-700, 2004.

6)       He, W., Halberstadt, C.R., and K.E. Gonsalves. Lithography application of a novel photoresist for patterning of cells. Biomaterials, 25:2055-2063, 2004.

7)       Emerich, D.F., Hemendinger, R. and C. Halberstadt. The testicular derived Sertoli cell: cellular immunoscience to enable transplantation. Cell Transplantation, 12:335-349, 2003.

8)       Gores, P.F., Hayes, D.H., Copeland, M.J., Korbutt, G., Halberstadt, C., Kirkpatrick, S.A., and R.V. Rajotte. Long-term survival of intratesticular porcine islets in non-immunosuppressed beagles. Transplantation, 15;75(5):613-618, March, 2003.

9)       He, W., Gonsalves, K., and C. Halberstadt. Synthesis, Characterization, and Preliminary Biological Study of Poly(3-(t-butoxycarbonyl)-N-vinyl-2-pyrrolidone). Biomacromolecules, 4(1):75-79, Jan 13, 2003.

10)    Halberstadt, C.R., Palsson, B.O., Midgley, A.R., and R.L. Curl. Optimization and Mathematical Modeling of the Transtubular Bioreactor for the Production of Monoclonal Antibody from a Hybridoma Cell Line. Biotechnology and Bioprocess Engineering, 7(3):163-170, 2002.

1)       KJL Burg, M Delnomdedieu, RJ Beiler, CR Culberson, KG Greene, CR Halberstadt, WD Holder, Jr, AB Loebsack, WD Roland, and GA Johnson. Application of Magnetic Resonance Microscopy to Tissue Engineering: A Polylactide Model. Journal of Biomedical Materials Research, 61(3):380-390, 2002.

2)       Halberstadt, C., Austin, C., Rowley, J., Culberson, C., Loebsack, A., Wyatt, S., Coleman, S., Blacksten, L., Burg, K., Mooney, D., and W. Holder Jr. A Hydrogel Material for Plastic and Reconstructive Applications Injected into the Subcutaneous Space of a Sheep.  Tissue Engineering, 8(2):309-319, 2002.

3)       Loebsack, A., Greene, K., Wyatt, S., Culberson, C., Austin, C., Beiler, R., Roland, W., Eiselt, P., Rowley, J., Burg, K., Mooney, D., Holder, W., and C. Halberstadt. In Vivo Characterization of a Porous Hydrogel Material for Use as a Tissue Bulking Agent.  Journal of Biomedical Materials Research, 57:575-581, 2001.

4)       Burg, K.J.L., Holder, W.D., Culberson, C.R., Beiler, R.J., Greene, K.G., Loebsack, A.B., Roland, W.D., Eiselt, P., Mooney, D.J., and C.R. Halberstadt.  Comparative Study of Seeding Methods for Three-Dimensional Polymeric Scaffolds. Journal of Biomedical Materials Research, 51(4):642-649, 2000

5)       Beiler, R.J., Greene, K.G., Culberson, C.R., Loebsack, A.B., Roland, W.R., Halberstadt, C.R., Holder, W.D., and K.J.L. Burg.  Absorbable Mesh Aids in Development of Discrete Tissue-Engineered Constructs.  Critical Reviews in Biomedical Engineering.  Volume 26 (#5&#6), 1999.

6)       Loebsack, AB, Halberstadt, CR, Holder, W.D., Jr., Gruber, H.E., Culberson C.R., Greene, K.G., Roland, W.D., and KJL Burg.  The Development of an Embedding Technique for Polylactide Sponges.  Journal of Biomaterials Science, 48:504-510, 1999.

7)       Burg, K.J.L., Holder, W.D., Culberson, C.R., Beiler, R.J., Greene, K.G., Loebsack, A.B., Roland, W.D., Mooney, D.J., and C.R. Halberstadt.  Parameters Affecting Cellular Adhesion to Polylactide Films.  Journal of Biomaterials Science – Polymer Edition, 10(2):147-161, 1999.

8)       Eiselt, P., Kim, B.-S., Chacko, B., Isenberg, B., Peters, M.C., Greene, K.G., Roland, W.D., Loebsack, A.B., Burg, K.J.L., Culberson, C., Halberstadt, C.R., Holder, W.D., and D.J. Mooney.  Development of Technologies Aiding Large-Tissue Engineering. Biotechnology Progress, Jan; 14(1): 134-140, 1998.

9)       Grande, D.A., Halberstadt, C., Naughton, G., Schwartz, R. and R. Manji: Evaluation of Matrix Scaffolds for Tissue Engineering of Articular Cartilage Grafts.  Journal of Biomedical Materials Research, 34, #2: 211-220, 1997.

10)    Sacks, M.S., Chuong, C.J., Petroll, W.M., Kwan, M., and C. Halberstadt: Collagen Fiber Architecture of a Cultured Dermal Tissue.  Journal of Biomechanical Engineering, 119, #1: 124-127, 1997.

11)    Halberstadt, C.R., Hardin, R., Bezverkov, K., Snyder, D., Allen, L. and L. Landeen: The In Vitro Growth of a Three-Dimensional Human Dermal Replacement Using a Single-Pass Perfusion System.  Biotechnology and Bioengineering, 43: 740-746, 1994.

12)    Landeen, L.K., Ziegler, F.C., Halberstadt, C.R., Cohen, C. and S.R. Slivka: Characterization of a Human Dermal Replacement.  Wounds, September-October, 1992.

13)    Halberstadt, C.R., Anderson, P., Bartel, R., Cohen, R. and G. Naughton: Physiological Cultured Skin Substitutes for Wound Healing in Materials Research Society Symposium Proceedings, 252: 323-330, 1992.

Book Chapters:

1)    Lee, K.Y., Halberstadt, C.R., Holder, W.D., and D.J. Mooney. Tissue Engineering for Breast Reconstruction. Principles of Tissue Engineering (2^nd Edition). Editors: R.Lanza, R. Langer and J. Vacanti. Academic Press, NY, NY: 409-425, 2000.

2)    Umar, Y., Thiyagarajan, M., Halberstadt, C., and K.E. Gonsalves. Patterning of Cells on Bioresist for Tissue Engineering Applications. Material Research Society Symposium Proceedings. Editors C. Laurencian and E. Botchwey. Volume 845, 2005.

Patents: (Partial Listing)

11)    Burg, K.J.L., Halberstadt, C.R., and Holder, W.D.: Absorbable Tissue Expander, U.S. Patent #6,66,893 received December 23, 2003.

12)    Eiselt, P., Halberstadt, C., Mooney, D., Yeh, J., Latvala, R., and J.A. Rowley. Preparing porous hydrogel products, U.S. Patent #6,511,650 received January 28, 2003.

13)    Naughton, B. A., Halberstadt, C.R., and B. Sibanda: Method for culturing three-dimensional tissue in diffusion gradient bioreactor and use thereof, U.S. Patent #6,218,182 received April 17, 2001.

14)    Burg, K.J.L., Halberstadt, C.R., and Holder, W.D.: Absorbable Tissue Expander, U.S. Patent #6,206,930 received March 27, 2001.

15)    Halberstadt, C.R.: Laminin 5 for Periodontal Treatment, U.S. Patent #6,034,068 received March 7, 2000.

16)    Naughton, B. A., Halberstadt, C.R., and B. Sibanda: Diffusion Gradient Bioreactor and Extracorporeal Liver Device, U.S. Patent #6,008,049 received December 28, 1999.

17)    Naughton, B. A., Halberstadt, C.R., and B. Sibanda: Diffusion Gradient Bioreactor and Extracorporeal Liver Device Using a Three-Dimensional Liver Tissue, U.S. Patent #5,827,729 received October 27, 1998.

18)    Halberstadt, C.R. and A.R. Midgley: Bioreactor System, U.S. Patent #5,081,035 received on January 14, 1992

Abstracts: (Partial listing)

1)       Umar, Y., Thiyagaragan, M., Halberstadt, C, and K. E. Gonsalves. Patterning of cells on bioresist for tissue engineering applications: Lithographic approach. American Chemical Society Meeting, San Diego, CA, March 13-17, 2005.

2)       Thiyagarajan, M, Gonsalves, KE, Umay, Y, and Halberstadt, CR. Microstructure determination of bioresists and application for 3D scaffold fabrication. Materials Research Society, Boston, MA, November 28 – December 3, 2004.

3)       Halberstadt^, CR, Williams, D, Curry, W, Bhatia, A, Emerich, D, Goddard, M, Vasconcellos, A, and Gores, P. The use of a subcutaneous device for islet engraftment and function in a diabetic rat model. Cell Transplantation Society, Boston, November 18-20, 2004.

4)       He W., Gonsalves K.E., and Halberstadt C.  The Development and Characterization of a Novel BIORESIST for the Spatial Organization of Mammalian Cells.  Materials Research Society, Boston, MA. Presented, December 4^th, 2003.

5)       Gonsalves, K.E., Halberstadt, C.R., He, W., and A. Ali.  Bioresist for Cell Patterning. Southern Biomedical Engineering Conference and Symposium on Aortic Valve Sparing Surgery, Charlotte, North Carolina. Accepted for presentation, September 26-28, 2003.

6)       Lyles M.B., Halberstadt C., Hemendinger R., Fiechtl J., Kellam, J.F., McAllister B., and Martell J. Use of a novel polymeric inorganic matrix in bone healing.  Presented at Cold Spring Harbor Tissue Engineering Meeting, Cold Spring harbor, New York, November 21-24, 2002.

7)       CR Halberstadt. Adipose Tissue Engineering. Presented at the Fourth Annual Southeastern Tissue Engineering Conference, Research Triangle Park, North Carolina, June 7, 2002

8)       Harold K.L., He W., Halberstadt C.R., Matthews B.D., Kercher K.W., Sing R.F., Heniford T. Fibroblast Adherence and Proliferation on Prosthetic Mesh In Vitro.  Presented at the American Hernia Society meeting, Tucson AZ, May 8-12, 2002.

9)       Hemendinger R., Swiggett J., Rounds D., Gores P. and Halberstadt C. Assessment of Viability of Both Mono-dispersed Cells and 3-Dimensional Multicellular Aggregates using Confocal Microscopy.  Presented at the Third Annual Tissue Engineering Society Meeting, Orlando, FL. December 1-3, 2000.

10)    Halberstadt C., Austin C., Rowley J., Culberson C., Loebsack A., Wyatt S., Coleman S., Blacksten L., Burg K., Mooney D., and Holder W. A Hydrogel Material for Plastic and Reconstructive Applications Injected into the Subcutaneous Space of a Sheep. Presented at the Third Annual Tissue Engineering Society Meeting, Orlando, FL. December 1-3, 2000.

11)    Halberstadt, CR, Mooney, DJ, Burg, KJL, Eiselt, P, Rowley, JA, Beiler, RJ, Roland, WD, Austin, CE, Culberson, CR, Greene, KG, Wyatt, S, Loebsack, AB, and Holder, WD Jr, The Design and Implementation of an Alginate Material for Soft Tissue Engineering.  Presented at the Sixth World Biomaterials Congress, Hawaii, Hawaii, May 15-20, 2000.

12)    Burg KJL, Austin CE, Mooney DJ, Eiselt P, Yeh J, Rowley JA, Culberson CR, Greene KG, Holder WD Jr., Loebsack AB, Wyatt S, and Halberstadt CR. Optimizing Microstructure of Porous Alginate-RGD beads for Tissue Engineering Application. Presented at the Sixth World Biomaterials Congress, Hawaii, Hawaii, May 15-20, 2000.

13)    Greene, KG, Burg, KJL, Austin, CE, Culberson, CR, Halberstadt, CR, Holder, WD Jr, Morton, DS, Wyatt, S, and Loebsack, AB.  The Development of a Seeding Method for a Porous Hydrogel Construct. Presented at the Sixth World Biomaterials Congress, Hawaii, Hawaii, May 15-20, 2000.

14)    Burg, K.J.L., Mikos, A.G., Beiler, R.J., Culberson, C.R., Greene, K.G., Loebsack, A.B., Roland, W.D., Wyatt, S., Halberstadt, C.R., Holder, W.D., Jr., and T.C. Burg.  Particulate Selection and Importance to Cell Adhesion in Solvent-Cast, Particulate-Leached Polymeric Constructs.  Presented at the Society for Biomaterials Meeting, Providence, Rhode Island, April 28 - May 2, 1999.

15)    Roland, WD, Holder, WD, Culberson, CR, Beiler, RJ, Burg, KJL, Greene, KG, Loebsack, AB, Wyatt, S, and CR Halberstadt.  Optimizing Cell Culture Time and Seeding Density on Porous, Absorbable Constructs.  Presented at the Tissue Engineering Society Meeting, Orlando, Florida, December 4-6, 1998.

16)    Burg, KJL., Holder, WD, Jr., Culberson, CR, Beiler, RJ, Greene, KG, Loebsack, AB, Roland, WD, and CR Halberstadt.  Selection of Seeding Methods Toward Enhanced Vascularization of Porous, Absorbable Constructs.  Presented at the Tissue Engineering Society Meeting, Orlando, Florida, December 4-6, 1998.

17)    Burg, KJL, Delnomdedieu, M, Beiler, RJ, Culberson, CR, Greene, KG, Loebsack, AB, Roland, WD, Wyatt, S, Halberstadt, CR, Holder, WD, Jr., and GA Johnson. Application of Magnetic Resonance Microscopy to Tissue Engineering.  Presented at the Tissue Engineering Society Meeting, Orlando, Florida, December 4-6, 1998.

18)    Greene, KG, Halberstadt, CR, Holder, WD, Jr., Culberson, CR, Beiler, RJ, Loebsack, AB, Roland, WD, Yeh, J, Mooney, DJ, and KJL Burg.  In Vivo Cellular Invasion of Novel Porous PLGA Matrices.  Presented at the Tissue Engineering Society Meeting, Orlando, Florida, December 4-6, 1998.

19)    Burg, KJL, Holder, WD, Jr., Culberson, CR, Beiler, RJ, Greene, KG, Loebsack, AB, Roland, WD, Eiselt, P, Mooney, DJ, and CR Halberstadt.  A Study of Tissue Engineering Seeding and Proliferation Methods. Presented to the Society for Biomaterials Annual Meeting, San Diego, California, April 22-26, 1998.

20)    Burg, K.J.L., Mooney, D.J., Halberstadt, C.R., Culberson, C.R., Black, M.C., Moore, A.L., Roland, W., and W. Holder.  Parameters Affecting Cellular Adhesion to Polyglycolide and Polylactide Porous Constructs.  Presented at the American Chemical Society Meeting, April 16-20, 1997, San Francisco, California.

21)    Sacks, M., Chuong, C.J., Halberstadt, C., and M. Kwan: Collagen Fiber Architecture of Cultured Dermal Tissue Measured Using Small Angle Light Scattering.  Presented at the meeting of The American Society of Mechanical Engineers, November 28-December 3, 1993, New Orleans, Louisiana.

22)    Landeen, L.K., Kidd, I.D., and C.R. Halberstadt: Extracellular Matrix Deposition is Influenced by Lactic Acid in a Human Dermal Replacement.  Presented at the meeting of the Congress on Cell and Tissue Culture, June 5-9, 1993, San Diego, CA.

23)    Hardin, R.J., Bezverkov, K.I., Snyder, D.A., and C.R. Halberstadt: The Growth of a Three-Dimensional Dermal Equivalent Using a Single-Pass Perfusion System.  Presented at the meeting of the Congress on Cell and Tissue Culture, June 5-9, 1993, San Diego, CA.

24)    Landeen, L.K., Halberstadt, C.R., King, B.D., and G.K. Naughton: A Novel Human Dermal Replacement: Characterization and Early Clinical Trials.  Presented at the meeting of the Society for Investigative Dermatology, April 4-9, 1993, Washington, D.C.

25)    Halberstadt, C.R., Hardin, R., Bezverkov, K., and M. Kwan: The Development of a Perfusion System for the Growth of a Three-Dimensional Dermal Equivalent.  Presented at the American Chemical Society meeting, March 28-31, 1993, Denver, CO.

26)    Landeen, L., Kidd, I.D., and C.R. Halberstadt: Effects of Lactic Acid on Cell Growth and Extracellular Matrix Deposition in a Human Dermal Replacement.  Presented at the Pan Pacific Regional Meeting of the International Society for Burn Injuries, February 22-26, 1993.

27)    Grande, D., Halberstadt, C., Schwartz, R., Linton, J., and G. Naughton: Evaluation of Extracellular Matrix Scaffolds for Engineering of Articular Cartilage Grafts.  Presented at the Meeting of the Orthopedic Research Society, February 15-18, 1993, San Francisco, CA.

28)    Halberstadt, C.R.: Tear Strength Properties of a Novel Cultured Dermal Tissue Model.  Presented at the Medical Research Forum on Wound Repair/Symposium on Advanced Wound Care, April 23-25, 1992, New Orleans, Louisiana.

29)    Grande, D., Halberstadt, C.R., Linton, J. and G. Naughton: A Culture System for the Three-Dimensional Growth of Cartilage.  Presented at the Keystone Tissue Engineering Symposium, April, 1992, Keystone, Colorado.

30)    Halberstadt, C.R., Slivka, S., Ziegler, F., Zimber, M.P. and R.K. Bartel: The Development, Characterization and Clinical Use of a Three-Dimensional Dermal Equivalent.  Presented at the Keystone Tissue Engineering Symposium, April, 1992, Keystone, Colorado.

31)    Cohen, R., Halberstadt, C.R., Cooper, M. and J. Hansbrough: Physiological Cultured Skin Substitutes for Wound Healing.  Presented at the Materials Research Society Meeting, December 2-6, 1991, Boston, MA.

32)    Slivka, S.R., Halberstadt, C.R., Landeen, L., Zimber, M.P. and R.L. Bartel: Characterization of a Three-Dimensional Cultured Human Skin Model.  Presented at the American Institute of Chemical Engineering Annual Meeting, November, 1991, Los Angeles, California.