Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2006-03-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000006783981981 |
| _version_ | 1819008684101992448 |
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| author | Ikuko Sugaya Tingyu Qu Kiminobu Sugaya George D. Pappas |
| author_facet | Ikuko Sugaya Tingyu Qu Kiminobu Sugaya George D. Pappas |
| author_sort | Ikuko Sugaya |
| collection | DOAJ |
| description | 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 preproenkephalin (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. |
| first_indexed | 2024-12-21T00:44:23Z |
| format | Article |
| id | doaj.art-e9a926301ac84ac2810ae9f3e89d3091 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T00:44:23Z |
| publishDate | 2006-03-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-e9a926301ac84ac2810ae9f3e89d30912022-12-21T19:21:35ZengSAGE PublishingCell Transplantation0963-68971555-38922006-03-011510.3727/000000006783981981Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in VitroIkuko Sugaya0Tingyu Qu1Kiminobu Sugaya2George D. Pappas3Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816-2364, USAThe Psychiatric Institute, Department of Psychiatry, and Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USABiomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, FL 32816-2364, USAThe Psychiatric Institute, Department of Psychiatry, and Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USAWe 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 preproenkephalin (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.https://doi.org/10.3727/000000006783981981 |
| spellingShingle | Ikuko Sugaya Tingyu Qu Kiminobu Sugaya George D. Pappas Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro Cell Transplantation |
| title | Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro |
| title_full | Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro |
| title_fullStr | Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro |
| title_full_unstemmed | Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro |
| title_short | Genetically Engineered Human Mesenchymal Stem Cells Produce Met-Enkephalin at Augmented Higher Levels in Vitro |
| title_sort | genetically engineered human mesenchymal stem cells produce met enkephalin at augmented higher levels in vitro |
| url | https://doi.org/10.3727/000000006783981981 |
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