Document Detail


Improving cell therapy--experiments using transplanted telomerase-immortalized cells in immunodeficient mice.
MedLine Citation:
PMID:  17123586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell therapy is the use of stem cells and other types of cells in various therapies for age-related diseases. Two issues that must be addressed before cell therapy could be used routinely in medicine are improved efficacy of the transplanted cells and demonstrated long-term safety. Desirable genetic modifications that could be made to cells to be used for cell therapy include immortalization with human telomerase reverse transcriptase (hTERT). We have used a model for cell therapy in which transplantation of adrenocortical cells restores glucocorticoid and mineralocorticoid hormone levels in adrenalectomized immunodeficient mice. In this model, clones of cells that had been immortalized with hTERT were shown to be able to replace the function of the animals' adrenal glands by forming vascularized tissue structures when cells were transplanted beneath the capsule of the kidney. hTERT-modified cells showed no tendency for neoplastic changes. Moreover, a series of experiments showed that hTERT does not cooperate with known oncoproteins in tumorigenesis either in adrenocortical cells or in human fibroblasts. Nevertheless, hTERT was required for tumorigenesis when cells were implanted subcutaneously rather than in the subrenal capsule space. Changes in gene expression make hTERT-modified cells more robust. Understanding these changes is important so as to be able to separately control immortalization and other desirable properties of cells that could be used in cell therapy. Alternatively, desirable properties of transplants might be provided by co-transplanted mesenchymal cells: mesenchymal cell-assisted cell therapy. For both hTERT modification and mesenchymal cell-assisted cell therapy, genomics approaches will be needed to define what genetic modifications are desirable and safe in cells used in cell therapy.
Authors:
Qin Huang; Meizhen Chen; Sitai Liang; Victor Acha; Dan Liu; Furong Yuan; Christina L Hawks; Peter J Hornsby
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2006-11-22
Journal Detail:
Title:  Mechanisms of ageing and development     Volume:  128     ISSN:  0047-6374     ISO Abbreviation:  Mech. Ageing Dev.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-15     Completed Date:  2007-04-20     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0347227     Medline TA:  Mech Ageing Dev     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  25-30     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Humans
Immunologic Deficiency Syndromes / therapy*
Mesenchymal Stem Cell Transplantation*
Mesenchymal Stromal Cells* / enzymology
Mice
Telomerase / genetics,  physiology*
Grant Support
ID/Acronym/Agency:
AG12287/AG/NIA NIH HHS; AG20752/AG/NIA NIH HHS; P01 AG020752/AG/NIA NIH HHS; P30 CA54174/CA/NCI NIH HHS; R37 AG012287/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.7.49/Telomerase
Comments/Corrections

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