Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients

ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In t...

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Autores principales:	Anna Sobuś, Bartłomiej Baumert, Monika Gołąb-Janowska, Piotr Kulig, Edyta Paczkowska, Karolina Łuczkowska, Dorota Rogińska, Alicja Zawiślak, Sławomir Milczarek, Bogumiła Osękowska, Wioletta Pawlukowska, Agnieszka Meller, Karolina Machowska-Sempruch, Agnieszka Wełnicka, Przemysław Nowacki, Bogusław Machaliński
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	amyotrophic lateral sclerosis lineage-negative cells cell therapy innate immunity complement system Medicine R
Acceso en línea:	https://doaj.org/article/b0ad234936694f92a088923edad79b3e
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spelling	oai:doaj.org-article:b0ad234936694f92a088923edad79b3e2021-11-25T18:00:52ZAdjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients10.3390/jcm102252512077-0383https://doaj.org/article/b0ad234936694f92a088923edad79b3e2021-11-01T00:00:00Zhttps://www.mdpi.com/2077-0383/10/22/5251https://doaj.org/toc/2077-0383ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In the present study, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin<sup>–</sup>) cells were performed every 6 weeks in 20 sporadic ALS patients. The concentrations of various complement components in the cerebrospinal fluid and plasma at different time points after cell injection were quantified using a Luminex multiplex. The results of the complement system were correlated with the level of leukocytes, neutrophils, lymphocytes, fibrinogen and CRP in the peripheral blood and the functional status of ALS patients using Norris and ALS-FRSr scales. The study showed a statistically significant decrease in plasma C3b concentration in all 7th days after cell application. In parallel, a peak decrease in neutrophil count and CRP level was observed on days 5–7, with a simultaneous maximum clinical improvement on days 7–28 of each Lin<sup>–</sup> cell administration. Adjuvant Lin<sup>–</sup> cell therapy appears to have the silencing potential on the complement-mediated immune system and thus suppress pro-inflammatory reactions responsible for neurodegeneration. However, further in-depth studies are necessary to address this issue.Anna SobuśBartłomiej BaumertMonika Gołąb-JanowskaPiotr KuligEdyta PaczkowskaKarolina ŁuczkowskaDorota RogińskaAlicja ZawiślakSławomir MilczarekBogumiła OsękowskaWioletta PawlukowskaAgnieszka MellerKarolina Machowska-SempruchAgnieszka WełnickaPrzemysław NowackiBogusław MachalińskiMDPI AGarticleamyotrophic lateral sclerosislineage-negative cellscell therapyinnate immunitycomplement systemMedicineRENJournal of Clinical Medicine, Vol 10, Iss 5251, p 5251 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	amyotrophic lateral sclerosis lineage-negative cells cell therapy innate immunity complement system Medicine R
spellingShingle	amyotrophic lateral sclerosis lineage-negative cells cell therapy innate immunity complement system Medicine R Anna Sobuś Bartłomiej Baumert Monika Gołąb-Janowska Piotr Kulig Edyta Paczkowska Karolina Łuczkowska Dorota Rogińska Alicja Zawiślak Sławomir Milczarek Bogumiła Osękowska Wioletta Pawlukowska Agnieszka Meller Karolina Machowska-Sempruch Agnieszka Wełnicka Przemysław Nowacki Bogusław Machaliński Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
description	ALS remains a fatal, neurodegenerative motor neuron disease. Numerous studies seem to confirm that innate immune system is involved in the pathophysiology of ALS. Hence, the assessment of the complement system and attempts to modify its activity remain the target of medical intervention in ALS. In the present study, three intrathecal administrations of autologous bone marrow-derived lineage-negative (Lin<sup>–</sup>) cells were performed every 6 weeks in 20 sporadic ALS patients. The concentrations of various complement components in the cerebrospinal fluid and plasma at different time points after cell injection were quantified using a Luminex multiplex. The results of the complement system were correlated with the level of leukocytes, neutrophils, lymphocytes, fibrinogen and CRP in the peripheral blood and the functional status of ALS patients using Norris and ALS-FRSr scales. The study showed a statistically significant decrease in plasma C3b concentration in all 7th days after cell application. In parallel, a peak decrease in neutrophil count and CRP level was observed on days 5–7, with a simultaneous maximum clinical improvement on days 7–28 of each Lin<sup>–</sup> cell administration. Adjuvant Lin<sup>–</sup> cell therapy appears to have the silencing potential on the complement-mediated immune system and thus suppress pro-inflammatory reactions responsible for neurodegeneration. However, further in-depth studies are necessary to address this issue.
format	article
author	Anna Sobuś Bartłomiej Baumert Monika Gołąb-Janowska Piotr Kulig Edyta Paczkowska Karolina Łuczkowska Dorota Rogińska Alicja Zawiślak Sławomir Milczarek Bogumiła Osękowska Wioletta Pawlukowska Agnieszka Meller Karolina Machowska-Sempruch Agnieszka Wełnicka Przemysław Nowacki Bogusław Machaliński
author_facet	Anna Sobuś Bartłomiej Baumert Monika Gołąb-Janowska Piotr Kulig Edyta Paczkowska Karolina Łuczkowska Dorota Rogińska Alicja Zawiślak Sławomir Milczarek Bogumiła Osękowska Wioletta Pawlukowska Agnieszka Meller Karolina Machowska-Sempruch Agnieszka Wełnicka Przemysław Nowacki Bogusław Machaliński
author_sort	Anna Sobuś
title	Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
title_short	Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
title_full	Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
title_fullStr	Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
title_full_unstemmed	Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients
title_sort	adjuvant lineage-negative cell therapy as a potential silencer of the complement-mediated immune system in als patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b0ad234936694f92a088923edad79b3e
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Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS Patients

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