Title

Genetically engineered human mesenchymal stem cells produce met-enkephalin at augmented higher levels in vitro

Authors

Authors

I. Sugaya; T. Y. Qu; K. Sugaya;G. D. Pappas

Comments

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Abbreviated Journal Title

Cell Transplant.

Keywords

preproenkephalin; gene transfection; human mesenchymal stem cells; autologous source; enkephalins; antinociception; MARROW STROMAL CELLS; ADRENAL-MEDULLARY TRANSPLANTS; BOVINE CHROMAFFIN; CELLS; RAT SPINAL-CORD; CANCER PAIN; PROENKEPHALIN; EXPRESSION; CATECHOLAMINES; DIFFERENTIATE; CULTURE; Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation

Abstract

We have reported that transplantation of adrenal medullary chromaffin cells that release endogenous opioid peptides into pain modulatory regions in the CNS produce significant antinociceptive effects in patients with terminal cancer pain. However, the usefulness of this procedure is minimal because the availability of human adrenal tissue is very limited. Alternative xenogeneic materials, such as porcine and bovine adrenal chromaffin cells present problems of immune rejection and possible pathogenic contamination. In an attempt to develop opioid peptide-producing cells of autologous origin, we have transfected human mesenchymal stem cells (hMeSCs) with a mammalian expression vector containing a fusion gene of green fluorescent protein (GFP) and human preprocrikephalin (hPPE), a precursor protein for enkephalin opioid peptides. Enkephalins are major neurotransmitters that play an important role in analgesia by activating peripheral opioid receptors. Following the establishment of stable transfection of hMeSCs, the expressions of hPPE and GFP were confirmed and the production of methionine enkephalin (Met-enkephalin) was significantly increased compared to control naive hMeSCs (p < 0.05). Our in vitro data demonstrated that genetically engineered hMeSCs with transfected hPPE gene can constitutively produce opioid peptide Met-enkephalin at an augmented high level. hMeSCs are relatively easy to isolate from a patient's bone marrow aspirates and expand in culture by repeated passages. Autologous hMeSCs would not require immunosuppression when transplanted back into the same patient. Through targeted gene manipulation such as hPPE gene transfection, this may offer a virtually unlimited safe cell supply for the treatment of opioid-sensitive pain in humans.

Journal Title

Cell Transplantation

Volume

15

Issue/Number

3

Publication Date

1-1-2006

Document Type

Article

Language

English

First Page

225

Last Page

230

WOS Identifier

WOS:000237492500003

ISSN

0963-6897

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