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...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-11-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/10/22/5251 |
| _version_ | 1797509878191751168 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:24:59Z |
| format | Article |
| id | doaj.art-b0ad234936694f92a088923edad79b3e |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T05:24:59Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-b0ad234936694f92a088923edad79b3e2023-11-22T23:48:36ZengMDPI AGJournal of Clinical Medicine2077-03832021-11-011022525110.3390/jcm10225251Adjuvant Lineage-Negative Cell Therapy as a Potential Silencer of the Complement-Mediated Immune System in ALS PatientsAnna Sobuś0Bartłomiej Baumert1Monika Gołąb-Janowska2Piotr Kulig3Edyta Paczkowska4Karolina Łuczkowska5Dorota Rogińska6Alicja Zawiślak7Sławomir Milczarek8Bogumiła Osękowska9Wioletta Pawlukowska10Agnieszka Meller11Karolina Machowska-Sempruch12Agnieszka Wełnicka13Przemysław Nowacki14Bogusław Machaliński15Department of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of Neurology, Pomeranian Medical University, 71-252 Szczecin, PolandDepartment of General Pathology, Pomeranian Medical University, 70-111 Szczecin, PolandALS 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.https://www.mdpi.com/2077-0383/10/22/5251amyotrophic lateral sclerosislineage-negative cellscell therapyinnate immunitycomplement system |
| spellingShingle | 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 Journal of Clinical Medicine amyotrophic lateral sclerosis lineage-negative cells cell therapy innate immunity complement system |
| title | 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_short | 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 |
| topic | amyotrophic lateral sclerosis lineage-negative cells cell therapy innate immunity complement system |
| url | https://www.mdpi.com/2077-0383/10/22/5251 |
| work_keys_str_mv | AT annasobus adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT bartłomiejbaumert adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT monikagołabjanowska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT piotrkulig adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT edytapaczkowska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT karolinałuczkowska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT dorotaroginska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT alicjazawislak adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT sławomirmilczarek adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT bogumiłaosekowska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT wiolettapawlukowska adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT agnieszkameller adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT karolinamachowskasempruch adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT agnieszkawełnicka adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT przemysławnowacki adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients AT bogusławmachalinski adjuvantlineagenegativecelltherapyasapotentialsilencerofthecomplementmediatedimmunesysteminalspatients |