Research abstract

Article abstract


Nature Biotechnology 20, 689 - 696 (2002)
Published online: 3 June 2002 | doi:10.1038/nbt703

Generation of histocompatible tissues using nuclear transplantation

Robert P. Lanza1, Ho Yun Chung2, James J. Yoo2, Peter J. Wettstein3, Catherine Blackwell1, Nancy Borson3, Erik Hofmeister3, Gunter Schuch2, Shay Soker2, Carlos T. Moraes4, Michael D. West1 & Anthony Atala2


Nuclear transplantation (therapeutic cloning) could theoretically provide a limitless source of cells for regenerative therapy. Although the cloned cells would carry the nuclear genome of the patient, the presence of mitochondria inherited from the recipient oocyte raises questions about the histocompatibility of the resulting cells. In this study, we created bioengineered tissues from cardiac, skeletal muscle, and renal cells cloned from adult bovine fibroblasts. Long-term viability was demonstrated after transplantation of the grafts into the nuclear donor animals. Reverse transcription-PCR (RT-PCR) and western blot analysis confirmed that the cloned tissues expressed tissue-specific mRNA and proteins while expressing a different mitochondrial DNA (mtDNA) haplotype. In addition to creating skeletal muscle and cardiac "patches", nuclear transplantation was used to generate functioning renal units that produced urinelike fluid and demonstrated unidirectional secretion and concentration of urea nitrogen and creatinine. Examination of the explanted renal devices revealed formation of organized glomeruli- and tubule-like structures. Delayed-type hypersensitivity (DTH) testing in vivo and Elispot analysis in vitro suggested that there was no rejection response to the cloned renal cells. The ability to generate histocompatible cells using cloning techniques addresses one of the major challenges in transplantation medicine.

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  1. Advanced Cell Technology, Worcester, MA 01605.
  2. Laboratory for Tissue Engineering and Cellular Therapeutics, Children's Hospital and Harvard Medical School, Boston, MA 02115.
  3. Departments of Surgery and Immunology, Mayo Clinic, Rochester, MN 55905.
  4. Department of Neurology, University of Miami School of Medicine, Miami, FL 33136.

Correspondence to: Anthony Atala2 e-mail: Anthony.atala@TCH.Harvard.edu