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Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells

Rifes, Pedro (författare)
Lund University,Lunds universitet,Human neural utvecklingsbiologi,Forskargrupper vid Lunds universitet,Human Neural Developmental Biology,Lund University Research Groups,University of Copenhagen,University of Copenhagen: Centre for Genre Research
Isaksson, Marc (författare)
Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,WCMM- Wallenberg center för molekylär medicinsk forskning,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Department of Experimental Medical Science,Faculty of Medicine,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,WCMM-Wallenberg Centre for Molecular Medicine
Rusimbi, Charlotte (författare)
University of Copenhagen
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Santoja, Adrian Ramón (författare)
University of Copenhagen
Wahlestedt, Jenny Nelander (författare)
Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Regeneration in Movement Disorders,Department of Experimental Medical Science,Faculty of Medicine,Developmental and Regenerative Neurobiology,Lund University Research Groups
Laurell, Thomas (författare)
Lund University,Lunds universitet,NanoLund: Centre for Nanoscience,Annan verksamhet, LTH,Lunds Tekniska Högskola,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,SEBRA Sepsis and Bacterial Resistance Alliance,Forskargrupper vid Lunds universitet,Acoustofluidics group,LTH profilområde: Nanovetenskap och halvledarteknologi,LTH profilområden,LTH profilområde: Teknik för hälsa,LU profilområde: Ljus och material,Lunds universitets profilområden,Other operations, LTH,Faculty of Engineering, LTH,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Lund University Research Groups,LTH Profile Area: Nanoscience and Semiconductor Technology,LTH Profile areas,Faculty of Engineering, LTH,LTH Profile Area: Engineering Health,Faculty of Engineering, LTH,LU Profile Area: Light and Materials,Lund University Profile areas
Kirkeby, Agnete (författare)
Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Human neural utvecklingsbiologi,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,Department of Experimental Medical Science,Faculty of Medicine,Human Neural Developmental Biology,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,University of Copenhagen
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 (creator_code:org_t)
2023
2023
Engelska 16 s.
Ingår i: Stem Cell Research & Therapy. - 1757-6512. ; 14:1
Relaterad länk:
http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • BackgroundVentral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic (DA) neurons with functionality relevant for cell replacement in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing.MethodsWe performed shotgun proteomics on cell culture supernatants from rostral and caudal VM progenitor cells to search for novel secreted biomarkers specific to DA progenitors from the caudal VM. Key hits were validated by qRT-PCR and ELISA.ResultsWe identified and validated novel secreted markers enriched in caudal VM progenitor cultures (CPE, LGI1 and PDGFC), and found these markers to correlate strongly with the expression of EN1, which is a predictive marker for successful graft outcome in DA cell transplantation products. Other markers (CNTN2 and CORIN) were found to conversely be enriched in the non-dopaminergic rostral VM cultures. Key novel ELISA markers were further validated on supernatant samples from GMP-manufactured caudal VM batches.ConclusionAs a non-invasive in-process quality control test for predicting correctly patterned batches of caudal VM DA cells during clinical manufacturing, we propose a dual ELISA panel measuring LGI1/CORIN ratios around day 16 of differentiation.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Biomedicinsk laboratorievetenskap/teknologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Biomedical Laboratory Science/Technology (hsv//eng)

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