Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy
Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In thi...
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| Veröffentlicht in: | Stem cells and development 2022-04, Vol.31 (7-8), p.163-175 |
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| creator | Cabanillas Stanchi, Karin Melanie Böhringer, Judith Strölin, Manuel Groeschel, Samuel Lenglinger, Katrin Treuner, Claudia Kehrer, Christiane Laugwitz, Lucia Bevot, Andrea Kaiser, Nadja Schumm, Michael Lang, Peter Handgretinger, Rupert Krägeloh-Mann, Ingeborg Müller, Ingo Döring, Michaela |
| description | Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 × 10
6
MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol·10
−6
and range 0.41–1.73 | MSCG: median 1.58 nmol·10
−6
and range 0.44–2.6;
P
|
| doi_str_mv | 10.1089/scd.2021.0352 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2642890603</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2642890603</sourcerecordid><originalsourceid>FETCH-LOGICAL-c252t-fa502da5bd2cbff61de1583afead23d8a81fc9a749f971156ea6e1682ba040783</originalsourceid><addsrcrecordid>eNqF0MtLxDAQBvAgiu-jV-nRS9c8mjY9yuILVjy4nss0mdJoXyZZZP97G3b16mnC8MvH8BFyxeiCUVXeem0WnHK2oELyA3LKpCxSJUV2GN9ZkQquihNy5v0HpTznKjsmJ0IKLigrT0l4wh7COI0Wg9XJW8A-WWLXJWsHg586GAIEOw7Jtw1t8oIeB91ue-hm6sY4o_aJHZJlazvj8I8G0G0kMXeFm8_RbP38Z2q3F-Sogc7j5X6ek_eH-_XyKV29Pj4v71ap5pKHtAFJuQFZG67rpsmZQSaVgAbBcGEUKNboEoqsbMqCMZkj5MhyxWugGS2UOCc3u9zJjV8b9KHqrdfzvTDguPEVzzOuSppTMdN0R7UbvXfYVJOzPbhtxWgVi67moqtYdBWLnv31PnpT92j-9G-zMxA7ENcwDJ3FGl34J_YHhw6NRg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2642890603</pqid></control><display><type>article</type><title>Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Cabanillas Stanchi, Karin Melanie ; Böhringer, Judith ; Strölin, Manuel ; Groeschel, Samuel ; Lenglinger, Katrin ; Treuner, Claudia ; Kehrer, Christiane ; Laugwitz, Lucia ; Bevot, Andrea ; Kaiser, Nadja ; Schumm, Michael ; Lang, Peter ; Handgretinger, Rupert ; Krägeloh-Mann, Ingeborg ; Müller, Ingo ; Döring, Michaela</creator><creatorcontrib>Cabanillas Stanchi, Karin Melanie ; Böhringer, Judith ; Strölin, Manuel ; Groeschel, Samuel ; Lenglinger, Katrin ; Treuner, Claudia ; Kehrer, Christiane ; Laugwitz, Lucia ; Bevot, Andrea ; Kaiser, Nadja ; Schumm, Michael ; Lang, Peter ; Handgretinger, Rupert ; Krägeloh-Mann, Ingeborg ; Müller, Ingo ; Döring, Michaela</creatorcontrib><description>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 × 10
6
MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol·10
−6
and range 0.41–1.73 | MSCG: median 1.58 nmol·10
−6
and range 0.44–2.6;
P
< 0.05), as well as significantly higher leukocyte (
P
< 0.05) and thrombocyte (
P
< 0.001) levels within 365 days of MSC application compared to CG patients. Statistically significant effects on acute GvHD, regeneration of immune cells, MRI changes, gross motor function, and clinical outcomes were not detected. In conclusion, the application of MSCs in pediatric MLD patients after allogeneic HSCT was safe and well tolerated. The two applications of 2 × 10
6
/kg allogeneic MSCs were followed by improved engraftment and hematopoiesis within the first year after HSCT. Larger, prospective trials are necessary to evaluate the impact of MSC application on engraftment and hematopoietic recovery.</description><identifier>ISSN: 1547-3287</identifier><identifier>EISSN: 1557-8534</identifier><identifier>DOI: 10.1089/scd.2021.0352</identifier><identifier>PMID: 35323019</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc., publishers</publisher><subject>Child ; Graft vs Host Disease - etiology ; Hematopoietic Stem Cell Transplantation - methods ; Humans ; Leukodystrophy, Metachromatic - etiology ; Leukodystrophy, Metachromatic - therapy ; Mesenchymal Stem Cell Transplantation - adverse effects ; Mesenchymal Stem Cells - physiology ; Original Research Reports ; Prospective Studies ; Retrospective Studies</subject><ispartof>Stem cells and development, 2022-04, Vol.31 (7-8), p.163-175</ispartof><rights>2022, Mary Ann Liebert, Inc., publishers</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c252t-fa502da5bd2cbff61de1583afead23d8a81fc9a749f971156ea6e1682ba040783</citedby><cites>FETCH-LOGICAL-c252t-fa502da5bd2cbff61de1583afead23d8a81fc9a749f971156ea6e1682ba040783</cites><orcidid>0000-0002-8134-7350</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35323019$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cabanillas Stanchi, Karin Melanie</creatorcontrib><creatorcontrib>Böhringer, Judith</creatorcontrib><creatorcontrib>Strölin, Manuel</creatorcontrib><creatorcontrib>Groeschel, Samuel</creatorcontrib><creatorcontrib>Lenglinger, Katrin</creatorcontrib><creatorcontrib>Treuner, Claudia</creatorcontrib><creatorcontrib>Kehrer, Christiane</creatorcontrib><creatorcontrib>Laugwitz, Lucia</creatorcontrib><creatorcontrib>Bevot, Andrea</creatorcontrib><creatorcontrib>Kaiser, Nadja</creatorcontrib><creatorcontrib>Schumm, Michael</creatorcontrib><creatorcontrib>Lang, Peter</creatorcontrib><creatorcontrib>Handgretinger, Rupert</creatorcontrib><creatorcontrib>Krägeloh-Mann, Ingeborg</creatorcontrib><creatorcontrib>Müller, Ingo</creatorcontrib><creatorcontrib>Döring, Michaela</creatorcontrib><title>Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy</title><title>Stem cells and development</title><addtitle>Stem Cells Dev</addtitle><description>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 × 10
6
MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol·10
−6
and range 0.41–1.73 | MSCG: median 1.58 nmol·10
−6
and range 0.44–2.6;
P
< 0.05), as well as significantly higher leukocyte (
P
< 0.05) and thrombocyte (
P
< 0.001) levels within 365 days of MSC application compared to CG patients. Statistically significant effects on acute GvHD, regeneration of immune cells, MRI changes, gross motor function, and clinical outcomes were not detected. In conclusion, the application of MSCs in pediatric MLD patients after allogeneic HSCT was safe and well tolerated. The two applications of 2 × 10
6
/kg allogeneic MSCs were followed by improved engraftment and hematopoiesis within the first year after HSCT. Larger, prospective trials are necessary to evaluate the impact of MSC application on engraftment and hematopoietic recovery.</description><subject>Child</subject><subject>Graft vs Host Disease - etiology</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Humans</subject><subject>Leukodystrophy, Metachromatic - etiology</subject><subject>Leukodystrophy, Metachromatic - therapy</subject><subject>Mesenchymal Stem Cell Transplantation - adverse effects</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Original Research Reports</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><issn>1547-3287</issn><issn>1557-8534</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0MtLxDAQBvAgiu-jV-nRS9c8mjY9yuILVjy4nss0mdJoXyZZZP97G3b16mnC8MvH8BFyxeiCUVXeem0WnHK2oELyA3LKpCxSJUV2GN9ZkQquihNy5v0HpTznKjsmJ0IKLigrT0l4wh7COI0Wg9XJW8A-WWLXJWsHg586GAIEOw7Jtw1t8oIeB91ue-hm6sY4o_aJHZJlazvj8I8G0G0kMXeFm8_RbP38Z2q3F-Sogc7j5X6ek_eH-_XyKV29Pj4v71ap5pKHtAFJuQFZG67rpsmZQSaVgAbBcGEUKNboEoqsbMqCMZkj5MhyxWugGS2UOCc3u9zJjV8b9KHqrdfzvTDguPEVzzOuSppTMdN0R7UbvXfYVJOzPbhtxWgVi67moqtYdBWLnv31PnpT92j-9G-zMxA7ENcwDJ3FGl34J_YHhw6NRg</recordid><startdate>20220401</startdate><enddate>20220401</enddate><creator>Cabanillas Stanchi, Karin Melanie</creator><creator>Böhringer, Judith</creator><creator>Strölin, Manuel</creator><creator>Groeschel, Samuel</creator><creator>Lenglinger, Katrin</creator><creator>Treuner, Claudia</creator><creator>Kehrer, Christiane</creator><creator>Laugwitz, Lucia</creator><creator>Bevot, Andrea</creator><creator>Kaiser, Nadja</creator><creator>Schumm, Michael</creator><creator>Lang, Peter</creator><creator>Handgretinger, Rupert</creator><creator>Krägeloh-Mann, Ingeborg</creator><creator>Müller, Ingo</creator><creator>Döring, Michaela</creator><general>Mary Ann Liebert, Inc., publishers</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8134-7350</orcidid></search><sort><creationdate>20220401</creationdate><title>Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy</title><author>Cabanillas Stanchi, Karin Melanie ; Böhringer, Judith ; Strölin, Manuel ; Groeschel, Samuel ; Lenglinger, Katrin ; Treuner, Claudia ; Kehrer, Christiane ; Laugwitz, Lucia ; Bevot, Andrea ; Kaiser, Nadja ; Schumm, Michael ; Lang, Peter ; Handgretinger, Rupert ; Krägeloh-Mann, Ingeborg ; Müller, Ingo ; Döring, Michaela</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c252t-fa502da5bd2cbff61de1583afead23d8a81fc9a749f971156ea6e1682ba040783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Child</topic><topic>Graft vs Host Disease - etiology</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Humans</topic><topic>Leukodystrophy, Metachromatic - etiology</topic><topic>Leukodystrophy, Metachromatic - therapy</topic><topic>Mesenchymal Stem Cell Transplantation - adverse effects</topic><topic>Mesenchymal Stem Cells - physiology</topic><topic>Original Research Reports</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cabanillas Stanchi, Karin Melanie</creatorcontrib><creatorcontrib>Böhringer, Judith</creatorcontrib><creatorcontrib>Strölin, Manuel</creatorcontrib><creatorcontrib>Groeschel, Samuel</creatorcontrib><creatorcontrib>Lenglinger, Katrin</creatorcontrib><creatorcontrib>Treuner, Claudia</creatorcontrib><creatorcontrib>Kehrer, Christiane</creatorcontrib><creatorcontrib>Laugwitz, Lucia</creatorcontrib><creatorcontrib>Bevot, Andrea</creatorcontrib><creatorcontrib>Kaiser, Nadja</creatorcontrib><creatorcontrib>Schumm, Michael</creatorcontrib><creatorcontrib>Lang, Peter</creatorcontrib><creatorcontrib>Handgretinger, Rupert</creatorcontrib><creatorcontrib>Krägeloh-Mann, Ingeborg</creatorcontrib><creatorcontrib>Müller, Ingo</creatorcontrib><creatorcontrib>Döring, Michaela</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cells and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cabanillas Stanchi, Karin Melanie</au><au>Böhringer, Judith</au><au>Strölin, Manuel</au><au>Groeschel, Samuel</au><au>Lenglinger, Katrin</au><au>Treuner, Claudia</au><au>Kehrer, Christiane</au><au>Laugwitz, Lucia</au><au>Bevot, Andrea</au><au>Kaiser, Nadja</au><au>Schumm, Michael</au><au>Lang, Peter</au><au>Handgretinger, Rupert</au><au>Krägeloh-Mann, Ingeborg</au><au>Müller, Ingo</au><au>Döring, Michaela</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy</atitle><jtitle>Stem cells and development</jtitle><addtitle>Stem Cells Dev</addtitle><date>2022-04-01</date><risdate>2022</risdate><volume>31</volume><issue>7-8</issue><spage>163</spage><epage>175</epage><pages>163-175</pages><issn>1547-3287</issn><eissn>1557-8534</eissn><abstract>Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder primarily affecting the white matter of the nervous system that results from a deficiency of the arylsulfatase A (ARSA). Mesenchymal stem cells (MSCs) are able to secrete ARSA and have shown beneficial effects in MLD patients. In this retrospective analysis, 10 pediatric MLD patients [mesenchymal stem cell group (MSCG)] underwent allogeneic hematopoietic stem cell transplantation (HSCT) and received two applications of 2 × 10
6
MSCs/kg bodyweight at day +30 and +60 after HSCT between 2007 and 2018. MSC safety, occurrence of graft-versus-host disease (GvHD), blood ARSA levels, chimerism, cell regeneration and engraftment, magnetic resonance imaging (MRI) changes, and the gross motor function were assessed within the first year of HSCT. The long-term data included clinical outcomes and safety aspects of MSCs. Data were compared to a control cohort of seven pediatric MLD patients [control group (CG)] who underwent HSCT only. The application of MSC in pediatric MLD patients after allogeneic HSCT was safe and well tolerated, and long-term potentially MSC-related adverse effects up to 13.5 years after HSCT were not observed. Patients achieved significantly higher ARSA levels (CG: median 1.03 nmol·10
−6
and range 0.41–1.73 | MSCG: median 1.58 nmol·10
−6
and range 0.44–2.6;
P
< 0.05), as well as significantly higher leukocyte (
P
< 0.05) and thrombocyte (
P
< 0.001) levels within 365 days of MSC application compared to CG patients. Statistically significant effects on acute GvHD, regeneration of immune cells, MRI changes, gross motor function, and clinical outcomes were not detected. In conclusion, the application of MSCs in pediatric MLD patients after allogeneic HSCT was safe and well tolerated. The two applications of 2 × 10
6
/kg allogeneic MSCs were followed by improved engraftment and hematopoiesis within the first year after HSCT. Larger, prospective trials are necessary to evaluate the impact of MSC application on engraftment and hematopoietic recovery.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc., publishers</pub><pmid>35323019</pmid><doi>10.1089/scd.2021.0352</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8134-7350</orcidid></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Child Graft vs Host Disease - etiology Hematopoietic Stem Cell Transplantation - methods Humans Leukodystrophy, Metachromatic - etiology Leukodystrophy, Metachromatic - therapy Mesenchymal Stem Cell Transplantation - adverse effects Mesenchymal Stem Cells - physiology Original Research Reports Prospective Studies Retrospective Studies |
| title | Hematopoietic Stem Cell Transplantation with Mesenchymal Stromal Cells in Children with Metachromatic Leukodystrophy |
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