Department of Stem Cell Bioengineering

Head
Professor Leonora Buzanska, PhD, DSc, phone +48 22 66 85 250, This email address is being protected from spambots. You need JavaScript enabled to view it.
zdjęcie strona

Secretariat
Agnieszka Włodarczyk, phone: +48 22 60 86 604, This email address is being protected from spambots. You need JavaScript enabled to view it.
Research staff
Marta Kot, PhD, phone: +48 22 60 86 563, This email address is being protected from spambots. You need JavaScript enabled to view it.
Wioletta Lech, PhD, phone: +48 22 60 86 563, This email address is being protected from spambots. You need JavaScript enabled to view it.
Paweł Leszczyński, PhD, phone +48 22 608 66 04, This email address is being protected from spambots. You need JavaScript enabled to view it.
Valery Zayat , PhD, phone: +48 22 60 86 407, This email address is being protected from spambots. You need JavaScript enabled to view it.
Marzena Zychowicz, PhD, phone: +48 22 60 86 563, This email address is being protected from spambots. You need JavaScript enabled to view it.
Zuzanna Kuczyńska, MSc, phone: +48 22 60 86 604, This email address is being protected from spambots. You need JavaScript enabled to view it.
Technical Staff
Hanna Winiarska, phone: +48 22 60 86 563, This email address is being protected from spambots. You need JavaScript enabled to view it.
PhD students
Michał Liput, MSc, phone: +48 22 60 86 604, This email address is being protected from spambots. You need JavaScript enabled to view it.
Erkan Metin MSc, phone: +48 22 60 86 604
Graduate students
Aleksandra Duchnowska (SGGW)
Zuzanna Siek (SGGW)

Research profile

  • Derivation of therapeutically competent stem cells: optimization of biomimetic culture conditions, „priming”, and biomimetic environment (three-dimensional culture, signaling molecules, and physiological normoxia)
  • Preclinical studies of neuroprotective and anti-inflammatory potential of human mesenchymal stem cells (hMSC) ex vivo (organotypic hippocampal and spinal cord slides) and in vivo ( focal brain injury in rat) 
  • The role of mitochondrial biogenesis during early neural development: research using brain organoids obtained from human induced pluripotent stem cells (hiPSCs)
  • Application of new methods of stem cell bioengineering (reporter lines, genome editing) and their niche (control of physicochemical properties of 3D scaffolds) to study the molecular mechanisms of early neural development
  • Geno- and embryo-toxicity induced by neurotoxins:: mechanistic and molecular mechanisms using human induced pluripotent stem cells (hiPSC) model of early development

Grants

  • Linking Metabolic Response of Mitochondrial Biogenesis Induction Via Alpha 7 Nicotinic Acetylcholine Receptor Agonist in Human Familial Alzheimer`s Disease Dorsal Forebrain Organoid Model” the MMRI Research Fund grant no. FBW-08/2023, PI: Erkan Metin, Msc, 2023-2024

  • "The effect of nuclear FGFR1 on the mitophagy and neural cell type specification in the human cortical organoid model", NCN PRELUDIUM 21, nr2022/45/N/NZ3/04202, PI: Michal Liput,Msc, Supervisor: prof. Leonora Bużańska,implementation period 2023-2025

  • "Molecular engineering of PPARGC1A for controlling neuronal to glial switch in the development of cortical brain organoids",NCN PRELUDIUM 21, nr2022/45/N/NZ1/02754, PI: Zuzanna Kuczynska, Msc, Supervisor: prof. Leonora Bużańska,implementation period 2023-2025

  • “Partial reprogramming of dopaminergic neurons in a model of cell aging dependent on pharmacological regulation of telomerase activity”, the MMRI Research Fund grant no. F-032, PI: Paweł Leszczyński, PhD, 2022-2023

  • “The impact of intrastriatal transplantation of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) on hippocampal neurogenesis in a rat model of stroke”, the MMRI Research Fund grant no. FBW 022/2021, PI: Marta Kot, PhD, 2021 – 2022
  • „Biomaterials and advanced physical techniques for regenerative cardiology and neurology”, COST BIONECA Action WG4 network, Program of European Collaboration in the Field of Scientific and Technical Research, PI: prof. Leonora Buzanska, implementation period 2017- 2021
  • „Effect of PGC1a on mitochondrial biogenesis and neural differentiation during the early stages of human brain organoid development”, NCN OPUS 18, nr 2019/35/B/NZ3/04383, PI: prof. Leonora Buzanska, implementation period 2020-2024
  • „ Molecular evaluation of neuroprotective and regenerative properties of WJ-MSC cells after transplantation into a damaged rat brain”, NCN PRELUDIUM 18, nr 2019/35/N/NZ5/03723, PI: Wioletta Lech, Msc, Supervisor: prof. Leonora Bużańska, implementation period 2020-2023
  • „Embryotoxicity and teratogenicity as a result of the DNA damage response in iPS cells: the effect of methylmercury chloride and low oxygen levels”, NCN Preludium 9, nr 2015/17/N/NZ7/04096, PI: Justyna Augustyniak, Ph.D., Supervisor: prof. Leonora Buzanska, implementation period 2015-2019
  • „The role of mechanotransduction in the regulation of stem cell immunomodulation”, MINIATURA 3, nr 2019/03/X/NZ3/01109, PI: Marzena Zychowicz, Ph.D., Realization period 2020-2021
  • „Generation of induced pluripotent cells (iPSCs) from patients with Dravet Syndrome for modeling neuronal plasticity in genetically inherited forms of epilepsy in children”, MINIATURA 3, nr 2019/03/X/NZ3/02139, PI: Valery Zayat, Ph.D., Realization period 2020-2021

Collaboration:
domestic

  • Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Poland. Prof. Piotr Stepien. Topic: The influence of mitochondrial biogenesis on early neural development of human induced pluripotent stem cells (hiPSC)
  • Centre of Biological and Chemical Sciences, University of Warsaw, Poland. Prof. Krystian Jazdzewski. Topic: Transcriptomics research using next-generation sequencing (RNA-Seq) for early neural differentiation of human iPSC cells
  •  Department of General Pathology, Pomeranian Medical University, Poland. Prof. Bogdan Machalinski, Rector of Pomeranian Medical University, Head of Department of General Pathology. Topic: "Innovative strategy for diagnostics, prevention and adiuvant therapy of selected neurodegenerative disorders in population of Polish ancestry”- Strategmed II collaboration
  • University of Warmia and Mazury in Olsztyn. Head of Division of Innovative Neurosurgery and Neurophysiology, Department of Neurosurgery and Stem Cell Research Laboratory in UWM. Prof. Wojciech Maksymowicz, Vice-Rector for the Medical Studies and Research. Topic: "Innovative strategy for diagnostics, prevention and adiuvant therapy of selected neurodegenerative disorders in population of Polish ancestry” - Strategmed II collaboration 
  • Laboratory of Molecular Bases of Aging, Nencki Institute of Experimental Biology, PAS. Prof. Ewa Sikora. Topic: “Unravelling and Combating Neurodevelopmental Disorders (NDD) Using Induced Pluripotent Stem Cells (iPSC) and Cerebral Organoids”

    international 
  • State University of New York in Buffalo, Molecular and Structural Neurobiology and Gene Therapy Lab. Prof. Michał Stachowiak, Director of Stem Cells Engraftment & In Vivo Analysis Facility, WNYSTEM State University of New York @ Buffalo. Topic: Studies on early neural development in the model of human cerebral organoids, in health and disease
  • Universita Degli Studi Di Milano, Milan, Italy, Prof. Francesca Caloni, Head of Department of Veterinary Medicine. Topic: „Genotoxic response to MeHgCl of human induced pluripotent stem cells during neuronal development”, scientific exchange, Canaletto project 2016-2018
  • Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Prof. Magdalena Zernicka-Goetz, Head of Mammalian Embryo and Stem Cell Group. Topic: “Mechanisms of early neural development in the model of in vitro human embryogenesis based on iPS cells in a chemically-defined 3D culture”, EMBO Fellowship collaboration
  • University of Modena e Reggio Emilia, Center for Regenerative Medicine, Modena, Włochy. Prof Graziella Pelegini. Topic: Developmental properties of human limbal stem cells at low oxygen tension conditions. Erasmus + collaboration
  • University Milano Bicocca, Mediolan oraz "Maggiore della Carità" University Hospital, Novara, Italy. Prof. Angelo Vescovi, dr Daniela Ferrari, prof. Letizzia Mazzini. Topic: ”Implementation of human neural stem cells for therapy of the CNS: preclinical studies”. COST BIONECA Action WG4 network collaboration

Research equipment

  • BioSpherix Xvivo X3 system for low oxygen culture
  • CytoSMART Lux 10X AACS-1001 Cystosmart TM Lux 10X System
  • Automatic cell counter (Invitrogen Countess automated cell counter C10227)
  • Fluorescence microscope system (Mikroscope Axiovert 40c, Zeiss, coupled with Canon
  • camera) 
  • Preparative and analytical HPLC (High-Performance Liquid Chromatography) with UV-VIS detector
  • Stereotaxic apparatus for rats with a microinjection pump

Research methods

  • in vitro – stem cell culture: on the 2D bioactive domains of defined geometry (A), pseudo-3D conditions (adherent culture of neural stem cells on a hydrogel of basement membrane proteins, matrigel) (B), cerebral organoids derived from human iPSC (non-adherent culture, under agitation conditions) (C), and 3D supporting scaffolds: keratin (D), collagen (E) , fibrin (F);
  • ex vivo - organotypic culture: model of injured hippocampal (G) and spinal cord (H);
  • in vivo - rat model of focal brain injury (I);
  • Molecular biology: RT-PCR, cloning, transduction, transfection, production of viral vectors, genome editing using the CRISPR/Cas9 method;
  • Determination of protein level and cytokine concentration (Western blot, ELISA/Luminex, ICC/IHC);
  • Pharmacokinetic and biochemical methods using the HPLC technique (e.g. metabolism of exogenous and endogenous substances);
  • Preclinical studies in rodents: rat model of stroke, mouse model of tumorigenicity (biosafety and biodistribution of MSCs and iPSCs, intracerebral transplantation of stem cells).

zbkm 2020

Selected publications

  • Tomecka E*, Lech W*, Zychowicz M, Sarnowska A, Murzyn M, Oldak T, Domanska-Janik K, Buzanska L, Rozwadowska N. Assessment of the Neuroprotective and Stemness Properties of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells under Variable (5% vs. 21%) Aerobic Conditions. Cells. 2021; 10(4):717. https://doi.org/10.3390/cells10040717

  • Naama M, Rahamim M, Zayat V, Sebban S, Radwan A, Orzech D, Lasry R, Ifrah A, Jaber M, Sabag O, Yassen H, Khatib A, Epsztejn-Litman S, Novoselsky-Persky M, Makedonski K, Deri N, Goldman-Wohl D, Cedar H, Yagel S, Eiges R, Buganim Y. Pluripotency-independent induction of human trophoblast stem cells from fibroblasts. Nat Commun. 2023 Jun 8;14(1):3359. doi: 10.1038/s41467-023-39104-1.

  • Zayat V, Kuczynska Z, Liput M, Metin E, Rzonca-Niewczas S, Smyk M, Mazurczak T, Goszczanska-Ciuchta A, Leszczynski P, Hoffman-Zacharska D, Buzanska L. The Generation of Human iPSC Lines from Three Individuals with Dravet Syndrome and Characterization of Neural Differentiation Markers in iPSC-Derived Ventral Forebrain Organoid Model. Cells. 2023 Jan 16;12(2):339. doi: 10.3390/cells12020339.

  • Book: “Human Neural Stem Cells: From Generation to Differentiation and Application”, Results and Problems in Cell Differentiation 66, 2018, Springer Nature, editor professor Leonora Buzanska (PDF)

  • Lech W, Sarnowska A, Kuczynska Z, Dabrowski F, Figiel-Dabrowska A, Domanska-Janik K, Buzanska L, Zychowicz M. Biomimetic microenvironmental preconditioning enhance neuroprotective properties of human mesenchymal stem cells derived from Wharton's Jelly (WJ-MSCs). Sci Rep. 2020 Oct 9;10(1):16946. doi: 10.1038/s41598-020-74066-0.

  • Sunderland P, Augustyniak J, Lenart J, Buzanska L, Carlessi L, Delia D, Sikora E. ATM-deficient neural precursors develop senescence phenotype with disturbances in autophagy. Mech Ageing Dev. 2020 Jul 1:111296. doi: 10.1016/j.mad.2020.111296.

  • Kosinski M, Figiel-Dabrowska A, Lech W, Wieprzowski L, Strzalkowski R, Strzemecki D, Cheda L, Lenart J, Domanska-Janik K, Sarnowska A. Bone Defect Repair Using a Bone Substitute Supported by Mesenchymal Stem Cells Derived from the Umbilical Cord. Stem Cells Int. 2020 5 kwietnia; 2020: 1321283. doi: 10.1155 / 2020/1321283. eCollection 2020.

  • Augustyniak J, Bertero A, Coccini T, Baderna D, Buzanska L, Caloni F. Organoids are promising tools for species-specific in vitro toxicological studies. J Appl Toxicol. 2019 Jun 5;39 (12):1610–1622. doi: 10.1002/jat.3815.

  • Bertero A, Augustyniak J, Buzanska L, Caloni F. Species-specific models in toxicology: in vitro epithelial barriers. Environ Toxicol Pharmacol. 2019 Jun 1;70:103203. doi:10.1016/j.etap.2019. 103203.

  • Augustyniak J, Lenart J, Lipka G, Stepien PP, Buzanska L. Reference Gene Validation via RT-qPCR for Human iPSC-Derived Neural Stem Cells and Neural Progenitors. Mol Neurobiol. 2019 Mar; 6 (10): 6820-6832. doi: 10.1007/s12035-019-1538-x.

  • Zychowicz M, Pietrucha K, Podobinska M, Kowalska-Wlodarczyk K, Lenart J, Augustyniak J, Buzanska L. The collagen scaffold as a carrier for hiPSC-derived neural stem cells, while restricting hiPSC growth. Front Biosci (Schol Ed). 2019 Mar 1;11:105-121.

  • Augustyniak J, Lenart J, Gaj P, Kolanowska M, Jazdzewski K, Stepien PP, Buzanska L. Bezafibrate Upregulates Mitochondrial Biogenesis and Influence Neural Differentiation of Human-Induced Pluripotent Stem Cells. Mol Neurobiol. 2019 Jun;56(6):4346-4363. doi: 10.1007/s12035-018-1368-2. Epub 2018 Oct 13. IF18 = 4,586

  • “Human Neural Stem Cells: From Generation to Differentiation and Application”. Results and Problems in Cell Differentiation 66, 2018, Springer Nature, editor: Leonora Bużańska

  • Janowska J, Gargas J, Ziemka-Nalecz M, Zalewska T, Buzanska L, Sypecka J. Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp Neurol. 2019 Sep;319:112813. doi: 10.1016/j.expneurol.2018.08.010. Epub 2018 Aug 30. Review. PMID: 30171864

  • Buzanska L, Zychowicz M, Kinsner-Ovaskainen A. Bioengineering of the Human Neural Stem Cell Niche: A Regulatory Environment for Cell Fate and Potential Target for Neurotoxicity. Results Probl Cell Differ. 2018;66:207-230. doi: 10.1007/978-3-319-93485-3_9.

  • Eve DJ, Sanberg PR, Buzanska L, Sarnowska A, Domanska-Janik K. Human Somatic Stem Cell Neural Differentiation Potential. Results Probl Cell Differ. 2018;66:21-87. doi: 10.1007/978-3-319-93485-3_2.

  • Janowska J, Gargas J, Ziemka-Nalecz M, Teresa Z, Buzanska L, Sypecka J. Directed glial differentiation and transdifferentiation for neural tissue regeneration. Exp Neurol. 2018 Aug 30. pii: S0014-4886(18)30401-1. doi: 10.1016/j.expneurol.2018.08.010. [Epub ahead of print]

  • Mazzini L, Ferrari D, Andjus PR, Buzanska L, Cantello R, De Marchi F, Gelati M, Giniatullin R, Glover JC, Grilli M, Kozlova EN, Maioli M, Mitrečić D, Pivoriunas A, Sanchez-Pernaute R, Sarnowska A, Vescovi AL. Advances in stem cell therapy for amyotrophic lateral sclerosis. BIONECA COST ACTION WG Neurology. Expert Opin Biol Ther. 2018 Aug;18(8):865-881. doi: 10.1080/14712598.2018.1503248

  • Kuzma-Kozakiewicz M, Marchel A, Kaminska A, Gawel M, Sznajder J, Figiel-Dabrowska A, Nowak A, Maj E, Krzesniak NE, Noszczyk BH, Domanska-Janik K, Sarnowska A. Intraspinal Transplantation of the Adipose Tissue-Derived Regenerative Cells in Amyotrophic Lateral Sclerosis in Accordance with the Current Experts' Recommendations: Choosing Optimal Monitoring Tools. Stem Cells Int. 2018 Aug 12;2018:4392017. doi: 10.1155/2018/4392017. eCollection 2018

  • Dabrowska S, Sypecka J, Jablonska A, Strojek L, Wielgos M, Domanska-Janik K, Sarnowska A. Neuroprotective Potential and Paracrine Activity of Stromal Vs. Culture-Expanded hMSC Derived from Wharton Jelly under Co-Cultured with Hippocampal Organotypic Slices. Mol Neurobiol. 2018 Jul;55(7):6021-6036. doi: 10.1007/s12035-017-0802-1

  • Huang H, Young W, Chen L, Feng S, Zoubi ZMA, Sharma HS, Saberi H, Moviglia GA, He X, Muresanu DF, Sharma A, Otom A, Andrews RJ, Al-Zoubi A, Bryukhovetskiy AS, Chernykh ER, Domańska-Janik K, Jafar E, Johnson WE, Li Y, Li D, Luan Z, Mao G, Shetty AK, Siniscalco D, Skaper S, Sun T, Wang Y, Wiklund L, Xue Q, You SW, Zheng Z, Dimitrijevic MR, Masri WSE, Sanberg PR, Xu Q, Luan G, Chopp M, Cho KS, Zhou XF, Wu P, Liu K, Mobasheri H, Ohtori S, Tanaka H, Han F, Feng Y, Zhang S, Lu Y, Zhang Z, Rao Y, Tang Z, Xi H, Wu L, Shen S, Xue M, Xiang G, Guo X, Yang X, Hao Y, Hu Y, Li J, Ao Q, Wang B, Zhang Z, Lu M, Li T. Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Cell Transplant. 2018 Feb;27(2):310-324. doi: 10.1177/0963689717746999

  • Janowska J, Gargas J, Ziemka-Nalecz M, Zalewska T, Buzanska L, Sypecka J. Directed glial differentiation and transdifferentiation for neural tissue regeneration. Experimental Neurology 2018 doi.org/10.1016/j.expneurol.2018.08.010

  • Pietrucha K, Zychowicz M, Podobinska M, Buzanska L. Functional properties of different collagen scaffolds to create a biomimetic niche for neurally committed human induced pluripotent stem cells (iPSC). Folia Neuropathol. 2017;55(2):110-123. doi: 10.5114/fn.2017.6857

  • Augustyniak J, Lenart J, Zychowicz M, Stepien PP, Buzanska L. Mitochondrial biogenesis and neural differentiation of human iPSC is modulated by idebenone in a developmental stage-dependent manner. Biogerontology. 2017;18(4):665-677. doi: 10.1007/s10522-017-9718-4

  • Augustyniak J, Lenart J, Zychowicz M, Lipka G, Gaj P, Kolanowska M, Stepien PP, Buzanska L. Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage. Toxicol in Vitro. 2017 Dec;45(Pt 3):434-444. doi: 10.1016/j.tiv.2017.05.017

  • Podobinska M, Szablowska-Gadomska I, Augustyniak J, Sandvig I, Sandvig A, Buzanska L. Epigenetic Modulation of Stem Cells in Neurodevelopment: The Role of Methylation and Acetylation. Front Cell Neurosci. 2017;7;11:23. doi: 10.3389/fncel.2017.00023

  • Sandvig I, Gadjanski I, Vlaski-Lafarge M, Buzanska L, Loncaric D, Sarnowska A, Rodriguez L, Sandvig A, Ivanovic Z. Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue. Stem Cells Dev. 2017;15;26(8):554-565. doi: 10.1089/scd.2016.0268

  • Krupska O, Sarnowska A, Fedorczyk B, Gewartowska M, Misicka A, Zablocka B, Beresewicz M. Ischemia/Reperfusion-Induced Translocation of PKCβII to Mitochondria as an Important Mediator of a Protective Signaling Mechanism in an Ischemia-Resistant Region of the Hippocampus. Neurochem Res. 2017;42(8):2392-2403. doi: 10.1007/s11064-017-2263-3

  • Drela K., Lech W., Figiel-Dabrowska A., Zychowicz M., Mikula M., Sarnowska A., Domanska-Janik K.Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture. Cytotherapy. 2016 Apr;18(4):497-509. doi: 10.1016/j.jcyt.2016.01.006

  • Obtulowicz P, Lech W, Strojek L, Sarnowska A, Domanska-Janik K. Induction of endothelial phenotype from Warton Jelly-derived MSC and comparison of their vaso- and neuro-protective potential with primary WJ-MSC in CA1 hippocampal region ex vivo. Cell Transplantation. 2016;25(4):715-27. doi: 10.3727/096368915X690369

  • Lech W., Figiel-Dabrowska A., Sarnowska A., Drela K., Obtulowicz P., Noszczyk B.H., Buzanska L., Domanska-Janik K. Phenotypic, Functional, and Safety Control at Preimplantation Phase of MSC-Based Therapy. Stem Cells Int. 2016;2016:2514917. doi: 10.1155/2016/2514917

  • Sypecka J, Sarnowska A. Mesenchymal cells of umbilical cord and umbilical cord blood as a source of human oligodendrocyte progenitors. Life Sci. 2015 Oct 15;139:24-9

  • Gornicka-Pawlak E, Janowski M, Jablonska A, Sypecka J, Domanska-Janik K. Complex assessment of distinct cognitive impairments following ouabain injection into the rat dorsoloateral striatum. Behav Brain Res. 2015 Aug 1;289:133-40. doi: 10.1016/j.bbr.2015.03.061

  • Sypecka J, Koniusz S, Kawalec M, Sarnowska A. The organotypic longitudinal spinal cord slice culture for stem cell study. Stem Cells Int. 2015;2015:471216

  • Janowski M, Walczak P, Kropiwnicki T, Jurkiewicz E, Domanska-Janik K, Bulte JWM, Lukomska B, Roszkowski M: Long-term MRI cell tracking after intraventricular delivery in a patient with global cerebral ischemia and prospects for magnetic navigation of stem cells within CSF. PLoS One 2014 Jun 11;9(2):e97631

  • Zychowicz M, Dziedzicka D, Mehn D, Kozlowska H, Kinsner-Ovaskainen A, Stepien PP, Rossi F, Buzanska L: Developmental stage dependent neural stem cells sensitivity to methylmercury chloride on different biofunctional surfaces. Toxicology in Vitro 2014:28:76-87 

  • Drela K, Sarnowska A, Siedlecka P, Szablowska-Gadomska I, Wielgos M, Jurga M, Lukomska B, Domanska-Janik K. Low oxygen atmosphere enhances proliferation and stemness properties of umbilical cord mesenchymal stem cell culture in HIF-dependent manner. Cytotherapy 2014:16:881-892

  • Augustyniak J, Zychowicz M, Podobinska M, Buzanska L. Reprogramming of the somatic cells: possible methods to derive the safe, clinical-grade human iPS cells. ANE 2014:74(4)