Reprogramming somatic cells to induced pluripotent stem (iPS) cells and directed differentiation opens up for studies on neural cells from patients. The Falk group is focusing on questions in early human neurogenesis.
Using reprogramming to model diseases of the human brain
Reprogramming somatic cells to induced pluripotent stem (iPS) cells and directed differentiation opens up for studies on neural cells from patients.
The Falk group is focusing on fundamental questions in early human neurogenesis:
- How do neural stem cells make their fate choices between self-renewal and differentiation? Between neurons and glia? How are these decisions hampered in neurodevelopmental and neuropsychiatric disorders? Are in vitro human neurogenesis, migration and maturation in 2D and/or 3D systems mimicking development in health and disease?
- The regenerative potential of iPS derived cell types and the routes forward to clinic
We build cellular models of the healthy and diseased human brain using reprogrammed patient cells. We derive patient specific iPS cells that are further differentiated into patient specific neuroepithelial stem (NES) cells. Both iPS and NES cell lines can be robustly expanded in culture and by applying efficient neuronal differentiation protocols we derive close to pure cultures of unlimited numbers of neurons. We use the cellular models to study proliferation, self-renewal, and differentiation potential as well as the function and subtype of derived neurons to uncover disease mechanisms.
The Falk lab is also driving translational projects investigating the regenerative potential of iPS cell derived neural cells in preclinical models with the aim to create ATMPs to take iPS derived cell to clinic. We have derived one of few clinical compliant GMP iPS cell lines that we have banked in a master bank and we are now investigating the route forward to clinic.
Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy.
Čančer M, Hutter S, Holmberg KO, Rosén G, Sundström A, Tailor J, et al
Cell Stem Cell 2019 Dec;25(6):855-870.e11
Ataxia in Patients With Bi-Allelic NFASC Mutations and Absence of Full-Length NF186.
Kvarnung M, Shahsavani M, Taylan F, Moslem M, Breeuwsma N, Laan L, et al
Front Genet 2019 ;10():896
Single cell analysis of autism patient with bi-allelic NRXN1-alpha deletion reveals skewed fate choice in neural progenitors and impaired neuronal functionality.
Lam M, Moslem M, Bryois J, Pronk RJ, Uhlin E, Ellström ID, et al
Exp. Cell Res. 2019 Oct;383(1):111469
Human iPS-Derived Astroglia from a Stable Neural Precursor State Show Improved Functionality Compared with Conventional Astrocytic Models.
Lundin A, Delsing L, Clausen M, Ricchiuto P, Sanchez J, Sabirsh A, et al
Stem Cell Reports 2018 03;10(3):1030-1045
An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis.
Shahsavani M, Pronk RJ, Falk R, Lam M, Moslem M, Linker SB, et al
Mol. Psychiatry 2018 07;23(7):1674-1684
Derivation of human iPS cell lines from monozygotic twins in defined and xeno free conditions.
Uhlin E, Rönnholm H, Day K, Kele M, Tammimies K, Bölte S, et al
Stem Cell Res 2017 01;18():22-25
Spider silk for xeno-free long-term self-renewal and differentiation of human pluripotent stem cells.
Wu S, Johansson J, Damdimopoulou P, Shahsavani M, Falk A, Hovatta O, et al
Biomaterials 2014 Oct;35(30):8496-502
A 3D Alzheimer's disease culture model and the induction of P21-activated kinase mediated sensing in iPSC derived neurons.
Zhang D, Pekkanen-Mattila M, Shahsavani M, Falk A, Teixeira AI, Herland A
Biomaterials 2014 Feb;35(5):1420-8
Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.
Tailor J, Kittappa R, Leto K, Gates M, Borel M, Paulsen O, et al
J. Neurosci. 2013 Jul;33(30):12407-22
Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells.
Fujimoto Y, Abematsu M, Falk A, Tsujimura K, Sanosaka T, Juliandi B, et al
Stem Cells 2012 Jun;30(6):1163-73
Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons.
Falk A, Koch P, Kesavan J, Takashima Y, Ladewig J, Alexander M, et al
PLoS ONE 2012 ;7(1):e29597