Theme I

In Vitro and In Vivo Tissue Engineering

Theme I, focused on in vitro and in vivo tissue engineering (TE), brings together a highly multidisciplinary group of experts. The core is formed by a Center of Excellence project Body-on-Chip Research at TAU (CoE-BoC, https://www.bodyonchip.fi/) in which we are ranked internationally among top 5 % in area of TE. Here, the national competence of the network is widened and strengthened by integrating internationally recognized research groups from UO with complementing expertise.

Technological, cell biology and clinical excellence in TE and in body-on-chip lies in the multidisciplinary research of internationally demonstrated expertise in

  • stem cell biology
  • biophysics
  • in vitro and in vivo tissue engineering
  • biomaterials
  • microsystem and bioimaging technologies
  • novel medical devices and related clinical expertise.

As examples, Theme I network has developed novel stem cell-based treatments for patients with cranio-maxillofacial bone defects and urinary incontinence, and for blindness (company formed currently); In the diagnostic area, biomarker-based technology is developed for customized treatment in ophthalmology; IPSC-derived cardiomyocytes have been utilized as drug testing platform for potential cardiac adverse effects; The formed Neuro Event Lab company provides personalized, accurate and scalable diagnostics for epilepsy patients with in-home monitoring system; and research in biomaterials has led to patent applications, publications and start-up companies.

Selected references

Junttila S, Saarela U, Halt K, Manninen A, Pärssinen H, Lecca MR, Brändli AW, Sims-Lucas S, Skovorodkin I, Vainio SJ. (2015) Functional genetic targeting of embryonic kidney progenitor cells ex vivo. Journal of the American Society of Nephrology : JASN, 26(5), 1126–1137. https://doi.org/10.1681/ASN.2013060584

Koivusalo L, Kauppila M, Ilmarinen T, Samanta S, Parihar VS, Miettinen S, Oommen OP,* Skottman H.* (2019) Tissue Adhesive Hyaluronic Acid Hydrogels for Sutureless Stem Cell Delivery and Regeneration of Corneal Epithelium and Stroma, Biomaterials, 2019, 225, 119516

Kuismanen K, Juntunen M, Narra Girish N, Tuominen H, Huhtala H, Nieminen K, Hyttinen J, Miettinen S. (2018) Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model. Stem Cells Transl Med. 2018 Mar;7(3):295-304. DOI: 10.1002/sctm.17-0208

Paakkola T, Salokas K, Miinalainen I, Lehtonen S, Manninen A, Kaakinen M, Ruddock LW, Varjosalo M, Kaarteenaho R, Uusimaa J, Hinttala R. (2018) Biallelic mutations in human NHLRC2 enhance myofibroblast differentiation in FINCA disease. Human molecular genetics, 27(24), 4288–4302. https://doi.org/10.1093/hmg/ddy298

Vuornos K, Ojansivu M, Koivisto JT, Häkkänen H, Belay B, Montonen T, Huhtala H, Kääriäinen M, Hupa L, Kellomäki M, Hyttinen J, Ihalainen JA, Miettinen S. (2019) Bioactive glass ions induce efficient osteogenic differentiation of human adipose stem cells encapsulated in gellan gum and collagen type I hydrogels. Mater Sci Eng C Mater Biol Appl. 2019 Jun;99:905-918. doi.org/10.1016/j.msec.2019.02.035

Karhula SS, Finnilä M, Rytky S, Cooper DM, Thevenot J, Valkealahti M, Pritzker K, Haapea M, Joukainen A, Lehenkari P, Kröger H, Korhonen RK, Nieminen HJ, Saarakkala S. (2020). Quantifying Subresolution 3D Morphology of Bone with Clinical Computed Tomography. Annals of biomedical engineering, 48(2), 595–605. https://doi.org/10.1007/s10439-019-02374-2

Kestilä I, Folkesson E, Finnilä MA, Turkiewicz A, Önnerfjord P, Hughes V, Tjörnstrand J, Englund M, Saarakkala S. (2019). Three-dimensional microstructure of human meniscus posterior horn in health and osteoarthritis. Osteoarthritis and cartilage, 27(12), 1790–1799. https://doi.org/10.1016/j.joca.2019.07.003

Lorite GS, Ylä-Outinen L, Janssen L, Pitkänen O, Joki T, Koivisto JT, Kellomäki M, Vajtai R, Narkilahti S, Kordas K. (2019) Carbon nanotube micropillars trigger guided growth of complex human neural stem cells networks. Nano Res. 12, 2894–2899. https://doi.org/10.1007/s12274-019-2533-2

Rytky S, Tiulpin A, Frondelius T, Finnilä M, Karhula SS, Leino J, Pritzker K, Valkealahti M, Lehenkari P, Joukainen A, Kröger H, Nieminen HJ, Saarakkala S. (2020). Automating three-dimensional osteoarthritis histopathological grading of human osteochondral tissue using machine learning on contrast-enhanced micro-computed tomography. Osteoarthritis and cartilage, 28(8), 1133–1144. https://doi.org/10.1016/j.joca.2020.05.002

Sorkio A, Koch L, Koivusalo L, Deiwick A, Miettinen S, Chichkov B, Skottman H. (2018) Human stem cell based corneal tissue mimicking structures using laser-assisted 3D bioprinting and functional bioinks. Biomaterials. 2018 Jul;171:57-71. doi: 10.1016/j.biomaterials.2018.04.034. Epub 2018 Apr 16.

Turunen S, Joki T, Hiltunen M, Ihalainen T, Narkilahti S, and Kellomäki M. (2017) Direct Laser Writing of Tubular Microtowers for 3D Culture of Human Pluripotent Stem-Cell Derived Neuronal Cells. ACS Appl Mater Interfaces. 2017 Aug 9;9(31):25717-25730. doi: 10.1021/acsami.7b05536

Halt KJ, Pärssinen HE, Junttila SM, Saarela U, Sims-Lucas S, Koivunen P, Myllyharju J, Quaggin S, Skovorodkin IN, Vainio SJ. (2016) CD146(+) cells are essential for kidney vasculature development. Kidney international, 90(2), 311–324. https://doi.org/10.1016/j.kint.2016.02.021

Hyvärinen T, Hagman S, Ristola M, Sukki L, Veijula K, Kreutzer J, Kallio P, Narkilahti S. (2019) Co-stimulation with IL-1β and TNF-α Induces an Inflammatory Reactive Astrocyte Phenotype with Neurosupportive Characteristics in a Human Pluripotent Stem Cell Model System. Scientific Reports 9 (1), 1694, November 2019. DOI: 10.1038/s41598-019-53414-9

Lappalainen OP, Karhula S, Haapea M, Kyllönen L, Haimi S, Miettinen S, Saarakkala S, Korpi J, Ylikontiola LP, Serlo WS, Sándor GK. (2016) Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds. Child’s nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, 32(4), 681–688. https://doi.org/10.1007/s00381-016-3017-2

Pelkonen A, Mzezewa R, Sukki L, Ryynänen T, Kreutzer J, Hyvärinen T, Vinogradov A, Aarnos L, Lekkala J, Kallio P, Narkilahti S. (2020) A modular brain-on-a-chip for modelling epileptic seizures with functionally connected human neuronal networks. Biosensors and Bioelectronics Volume 168, 15 November 2020. https://doi.org/10.1016/j.bios.2020.112553.

Bentham J, Di Cesare M, Bilano V, and 1,020 more authors. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128·9 million children, adolescents, and adults. Lancet 2017. Volume 390, Issue 10113, 16–22 December 2017, Pages 2627-2642 https://doi.org/10.1016/S0140-6736(17)32129-3

Das Gupta S, Finnilä M, Karhula SS, Kauppinen S, Joukainen A, Kröger H, Korhonen RK, Thambyah A, Rieppo L, Saarakkala S. (2020) Raman microspectroscopic analysis of the tissue-specific composition of the human osteochondral junction in osteoarthritis: A pilot study. Acta biomaterialia, 106, 145–155. https://doi.org/10.1016/j.actbio.2020.02.020

Lahti AL, Kujala VJ, Chapman H, Koivisto AP, Pekkanen-Mattila M, Kerkelä E, Hyttinen J, Kontula K, Swan H, Conklin BR, Yamanaka S, Silvennoinen O, Aalto-Setälä K. Model for long QT syndrome type 2 using human iPS cells demonstrates arrhythmogenic characteristics in cell culture. Dis Model Mech. 2012 Mar;5(2):220-30.

Shah D, Virtanen L, Prajapati C, Kiamehr M, Gullmets J, West G, Kreutzer J, Pekkanen-Mattila M, Heliö T, Kallio P, Taimen P, Aalto-Setälä K. Modeling of LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cells. Cells.  2019 Jun 15;8(6):594. doi: 10.3390/cells8060594.

Uusimaa J, Kaarteenaho R, Paakkola T, Tuominen H, Karjalainen MK, Nadaf J, Varilo T, Uusi-Mäkelä M, Suo-Palosaari M, Pietilä I, Hiltunen AE, Ruddock L, Alanen H, Biterova E, Miinalainen I, Salminen A, Soininen R, Manninen A, Sormunen R, Kaakinen M, Hinttala R. (2018) NHLRC2 variants identified in patients with fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA): characterisation of a novel cerebropulmonary disease. Acta neuropathologica, 135(5), 727–742. https://doi.org/10.1007/s00401-018-1817-z

Vidal B, Cascão R, Finnilä M, Lopes IP, Saarakkala S, Zioupos P, Canhão H, Fonseca JE. (2018) Early arthritis induces disturbances at bone nanostructural level reflected in decreased tissue hardness in an animal model of arthritis. PloS one, 13(1), e0190920. https://doi.org/10.1371/journal.pone.0190920

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