Erik Sundström group

Neural Cell Therapy and Repair

Research focus

Tissue sections through a 5.5 mm long branched cyst in a rat with post-traumatic syringomyelia.

The aim of our research is to investigate the potential of regenerative cell therapy, and how cell therapy can be applied for spinal cord injury. We have chosen mainly to focus on chronic spinal cord injury and a condition called post-traumatic syringomyelia (PTS). Persons with spinal cord injury may develop PTS years after injury. PTS is characterized by expanding cysts in the injured spinal cord that cause further destruction of the nervous tissue, and further loss of motor and sensory functions, increased spasticity and chronic pain.

Our hypothesis is that better treatment can be achieved by combining surgery with transplantation of neural stem cells. Our primary goal is to develop a treatment by which stem cells injected in the area of the cysts - in conjunction with the surgical treatment - induce a permanent collapse of the cysts that prevents further cyst expansion. The secondary goal is to replace the nerve cells that died after the spinal cord injury with differentiated cells derived from transplanted stem cells.

We have developed a reliable rat model of PTS that shares the important features with the clinical situation, and used this experimental model to analyze the mechanisms of effects of cell therapy as well as the processes involved in the cyst expansion. We have recently published results showing the efficiency of human neural stem cells transplanted to rat PTS cysts, and the different therapeutic effects that contribute to the regenerative effect of transplanted neural stem cells.

With our focus on cell therapy for regenerative treatments in the central nervous system, we are also investigating the normal development of human stem and progenitor cells. We analyze the normal development of the human spinal cord using a multi-omics strategy, as well as cultured human stem and progenitor cells. By integrating these results we can determine what molecular mechanisms that control the fate specification and differentiation of human spinal stem cells. The project is a part of the Human Developmental Cell Atlas consortium and the Human Cell Atlas initiative (https://hdca-sweden.scilifelab.se ; https://www.humancellatlas.org )

Group members

Erik Sundström

Principal researcher

Zjanna Alekseenko

Research Specialist

Xiaofei Li

Assistant professor

Yuxi Guo

Research assistant

Selected scientific publications

Decoding spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin. Li X, Andrusivova Z, Czarnewski P, Mattsson Langseth C, Andersson A, Liu Y, Gyllborg D, Braun E, Larsson L, Hu L, Alekseenko Z, Lee H, Avenel C, Kopp Kallner H, Åkesson E, Adameyko I, Nilsson M, Linnarsson S, Lundeberg J, Sundström E.
bioRxiv 

Stem Cell Therapies for Central Nervous System Trauma: The 4 Ws-What, When, Where, and Why.
Li X, Sundström E
Stem Cells Transl Med 2022 03;11(1):14-25

Multiple therapeutic effects of human neural stem cells derived from induced pluripotent stem cells in a rat model of post-traumatic syringomyelia.
Xu T, Li X, Guo Y, Uhlin E, Holmberg L, Mitra S, Winn D, Falk A, Sundström E
EBioMedicine 2022 Mar;77():103882

Developmental landscape of human forebrain at a single-cell level identifies early waves of oligodendrogenesis.
van Bruggen D, Pohl F, Langseth CM, Kukanja P, Lee H, Albiach AM, Kabbe M, Meijer M, Linnarsson S, Hilscher MM, Nilsson M, Sundström E, Castelo-Branco G
Dev Cell 2022 06;57(11):1421-1436.e5

A roadmap for the Human Developmental Cell Atlas.
Haniffa M, Taylor D, Linnarsson S, Aronow BJ, Bader GD, Barker RA, Camara PG, Camp JG, Chédotal A, Copp A, Etchevers HC, Giacobini P, Göttgens B, Guo G, Hupalowska A, James KR, Kirby E, Kriegstein A, Lundeberg J, Marioni JC, Meyer KB, Niakan KK, Nilsson M, Olabi B, Pe'er D, Regev A, Rood J, Rozenblatt-Rosen O, Satija R, Teichmann SA, Treutlein B, Vento-Tormo R, Webb S,
Nature 2021 09;597(7875):196-205

In Vitro Study of Human Immune Responses to Hyaluronic Acid Hydrogels, Recombinant Spidroins and Human Neural Progenitor Cells of Relevance to Spinal Cord Injury Repair.
Lin C, Ekblad-Nordberg Å, Michaëlsson J, Götherström C, Hsu CC, Ye H, Johansson J, Rising A, Sundström E, Åkesson E
Cells 2021 07;10(7):

Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia.
Xu N, Xu T, Mirasol R, Holmberg L, Vincent PH, Li X, Falk A, Benedikz E, Rotstein E, Seiger Å, Åkesson E, Falci S, Sundström E
Neurotherapeutics 2021 04;18(2):1257-1272

Single-cell transcriptomics of human embryos identifies multiple sympathoblast lineages with potential implications for neuroblastoma origin.
Kameneva P, Artemov AV, Kastriti ME, Faure L, Olsen TK, Otte J, Erickson A, Semsch B, Andersson ER, Ratz M, Frisén J, Tischler AS, de Krijger RR, Bouderlique T, Akkuratova N, Vorontsova M, Gusev O, Fried K, Sundström E, Mei S, Kogner P, Baryawno N, Kharchenko PV, Adameyko I
Nat Genet 2021 05;53(5):694-706

SCRINSHOT enables spatial mapping of cell states in tissue sections with single-cell resolution.
Sountoulidis A, Liontos A, Nguyen HP, Firsova AB, Fysikopoulos A, Qian X, Seeger W, Sundström E, Nilsson M, Samakovlis C
PLoS Biol 2020 11;18(11):e3000675

A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart.
Asp M, Giacomello S, Larsson L, Wu C, Fürth D, Qian X, Wärdell E, Custodio J, Reimegård J, Salmén F, Österholm C, Ståhl PL, Sundström E, Åkesson E, Bergmann O, Bienko M, Månsson-Broberg A, Nilsson M, Sylvén C, Lundeberg J
Cell 2019 Dec;179(7):1647-1660.e19

RNA velocity of single cells.
La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V, Lidschreiber K, Kastriti ME, Lönnerberg P, Furlan A, Fan J, Borm LE, Liu Z, van Bruggen D, Guo J, He X, Barker R, Sundström E, Castelo-Branco G, Cramer P, Adameyko I, Linnarsson S, Kharchenko PV
Nature 2018 08;560(7719):494-498

Neuroprotective effects of human spinal cord-derived neural precursor cells after transplantation to the injured spinal cord.
Emgård M, Piao J, Aineskog H, Liu J, Calzarossa C, Odeberg J, et al
Exp Neurol 2014 Mar;253():138-45

Detailed expression analysis of regulatory genes in the early developing human neural tube.
Marklund U, Alekseenko Z, Andersson E, Falci S, Westgren M, Perlmann T, et al
Stem Cells Dev 2014 Jan;23(1):5-15

A sensitive and reliable test instrument to assess swimming in rats with spinal cord injury.
Xu N, Åkesson E, Holmberg L, Sundström E
Behav Brain Res 2015 Sep;291():172-183

Human neural progenitor cells in central nervous system lesions.
Åkesson E, Sundström E
Best Pract Res Clin Obstet Gynaecol 2016 Feb;31():69-81

Wnt/β-Catenin Stimulation and Laminins Support Cardiovascular Cell Progenitor Expansion from Human Fetal Cardiac Mesenchymal Stromal Cells.
Månsson-Broberg A, Rodin S, Bulatovic I, Ibarra C, Löfling M, Genead R, et al
Stem Cell Reports 2016 Apr;6(4):607-617

Ascl1 Is Required for the Development of Specific Neuronal Subtypes in the Enteric Nervous System.
Memic F, Knoflach V, Sadler R, Tegerstedt G, Sundström E, Guillemot F, et al
J Neurosci 2016 Apr;36(15):4339-50

Fetal CD103+ IL-17-Producing Group 3 Innate Lymphoid Cells Represent the Dominant Lymphocyte Subset in Human Amniotic Fluid.
Marquardt N, Ivarsson MA, Sundström E, Åkesson E, Martini E, Eidsmo L, et al
J Immunol 2016 10;197(8):3069-3075

Expression of Pluripotency Markers in Nonpluripotent Human Neural Stem and Progenitor Cells.
Vincent PH, Benedikz E, Uhlén P, Hovatta O, Sundström E
Stem Cells Dev 2017 06;26(12):876-887

Transcription and Signaling Regulators in Developing Neuronal Subtypes of Mouse and Human Enteric Nervous System.
Memic F, Knoflach V, Morarach K, Sadler R, Laranjeira C, Hjerling-Leffler J, et al
Gastroenterology 2018 02;154(3):624-636

Differences in proliferation rate between CADASIL and control vascular smooth muscle cells are related to increased TGFβ expression.
Panahi M, Yousefi Mesri N, Samuelsson EB, Coupland KG, Forsell C, Graff C, et al
J Cell Mol Med 2018 06;22(6):3016-3024

 

Dissertations

TIngting Xu, 2022: Neural stem cell therapy and inflammation status of post-traumatic syringomyelia

Per Henrik Vincent, 2017: Specification and potency of neural stem cells for clinical transplantation

Ning Xu, 2015: Assessment of rat spinal cord injury models