Authors: | Lanza, R.; Shieh, J.H.; Wettstein, P. J.; Sweeney, R. W.; Wu, K.; Weisz, A.; Borson, N.; Henderson, B.; West, M. D.; Moore, M. A. S. |
Article Title: | Long-term bovine hematopoietic engraftment with clone-derived stem cells |
Abstract: | Therapeutic cloning by somatic cell nuclear transfer offers potential for treatment of a wide range of degenerative disease. Nuclear transplantation with Meor-marked somatic nuclei from 10-13-year-old cows was used to generate cloned bovine fetuses. Clone fetal liver (FL) hematopoietic stem cells (HSC) were transplanted into two busulfan-treated and one untreated nuclear donor cows. Hematopoiesis was monitored over 13-16 months by in vitro progenitor and HSC assays. Chimerism was demonstrated by PCR in blood, marrow, lymph nodes, and endothelium, peaking at levels of 9-17% in blood granulocytes but at lower levels in lymphocyte subsets (0.1-0.01%). Circulating progenitors showed high levels of chimerism (up to 60% neo r+) with persisting fetal features. At sacrifice, the animal that had no pre-transplant myelosupression showed persisting donor cells in blood and lymph nodes, and in marrow 0.25% of progenitor cells and a detectable fraction of stem cells were neo r+. The fetal HSC showed a 10-fold competition advantage over adult HSC. Cloning generated histocompatible HSC capable of long-term multilineage engraftment in a large animal model. © Mary Ann Liebert, Inc. |
Keywords: | controlled study; busulfan; nonhuman; lymph nodes; polymerase chain reaction; animal cell; animals; bone marrow cells; cells, cultured; somatic cell; bone marrow; bone marrow suppression; animal experiment; stem cell transplantation; animalia; chimera; molecular cloning; liver; endothelium, vascular; lymph node; cell isolation; hematopoietic stem cells; long term care; base sequence; hematopoiesis; cattle; hematopoietic stem cell; graft rejection; graft survival; dna primers; immunosuppressive treatment; endothelium; clone cells; degenerative disease; granulocyte; embryo culture; histocompatibility; bovinae; cell nucleus transplantation; fetus liver; cow |
Journal Title: | Cloning and Stem Cells |
Volume: | 7 |
Issue: | 2 |
ISSN: | 1536-2302 |
Publisher: | Mary Ann Liebert, Inc |
Date Published: | 2005-01-01 |
Start Page: | 95 |
End Page: | 106 |
Language: | English |
DOI: | 10.1089/clo.2005.7.95 |
PUBMED: | 15971983 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 24 October 2012" - "CODEN: CSCLB" - "Source: Scopus" |