regenerative medicine rOadmap 1.1 Regenerative medicine development roadmap is an essential tool for increasing the scope of research and attracting potential investors. dEVELOPERs: tissuE EnginEERing MEthOds dEVELOPMEnt Mikhail Batin (Science for Life Extension Foundation); Elena Kokurina (Science for Life Extension Bionics tissue Engineering (BitE) Bioprinting Foundation); Maria Konovalenko (Science for Life Extension Foundation); Real-time cellular interrogation technology: Monitoring of SC implants in the recipient organ Diagnostic devices for targeting biomarkers indicative of cellular disorders OrganizatiOnal aSpect 3D bioprinters development Alexander sprygin (PhD, Federal Centre for Animal Real-time tracking of migration, proliferation Intrabody rapid SC activation for formating tissue or organ fluorescent microscopy Microfluidic platforms Targeting of cancer-specific cellswith Tetrahymena Health, Vladimir); and fate of stem cells implanted in the group I intron ribozyme for detection of amiloidoo- for real-time imaging myocardium Maria thomas (PhD, Institute of clinical genic protein states Magnetic resonance Optic Replacement of the cancer- Selective delivery of Scale up technology legal issues reimburcements Быстрая активация СК для формирования ткани или органа pharmacology Robert Bosch Stiftung, Stuttgart); Maria tutukina (PhD, Dep. of Functional genomics Alternating current scanning Single-cell analysis of intracellular compounds imaging scan microscopy specific transcript with a a cytotoxin gene into commercialization Increase the number of available SC both in situ and in peripheral circulation (recruitmet factors) new (non-cancer) transcript a cancer cell Formation of 3D-heterocellular and cellular stress, Institute of Cell Biophysics RAS, electrochemical microscopy and changes in intracel- Generation of 2D- and 3D-homocel- (AC-SECM) for real-time lular compounds Through the expression of а labelled reporter lular cell aggregates: cell aggregates: Moscow); observation of living cells gene (Na/I symporter, D-luciferin, etc.) • simple models of artificial skin • sheets and tubes Alexei ulasov (Department of Molecular Genetics Granulocyte colony-stimulating factor (G-CSF) • Cubes and rings, and neural tubes Monitoring of host- Nanoparticles for detection • simplified bone marrow of Intracellular Transport, Institute of Gene Biology Tissue microarrays: real- Positron emission tomography and/or of a target and drug delivery • Rods and branching rods time monitoring of expres- pathogen interactions single photon emission tomography • Embryoid bodies • tissue-engineered vascular RAS, Moscow); Scientific aSpect sion of tumor supressor and cellular signaling grafts dmitry Chistyakov (PhD, D.Sci., State Research genes (p16, p53, RB) Non-radioactive labeling for detection Superparamagnetic Gold and silver Institute of Genetics and Selection of Industrial iron oxide nanopar- nanoparticles in detection ticles for detection of of a specific DNA Activation of a permissive situation of wound healing Formation of intermediate Microorganisms, Moscow); cancer cells, viruses, (Permissive factors) Generation of three-dimentional diameter branching tubes and sequence, bacterium, virus, Maria shkrob (PhD, Institute of Bioorganic Micro-electromechanical system (Bio-MEMS) pathogenic bacteria, antibody, etc. vascularized microtissue and tissue large tubes (macrovessels) devices for studying cultivated microtubules etc. (microvascular networks): Chemistry RAS, Moscow); Development of biomarkers of aging, in bioartificial muscle engineering diagnostic mathematical culturing in bioreactors Trauma cytokines release control, such as Paolo Macchiarini (MD, PhD, professor, department viability, health and pathologies modeling data bases IL-6, IL-1β and TNF-α • 3D-vascularized cardiac of regenerative surgery and biotransplantation, platforms and synthetic media muscle Development of three-dimen- tional vascularized organ University of Florence, Hospital Clinic University of Barcelona); Mikhail Paltsev (academician RAS and RAMS, I.M. Sechenov Moscow Medical Academy) Control of SC shifting towards a commitment Supporting tiSSue (Commitment factors) Preservation of regional SC of a young organism cell tHerapy Healing therapies Initiator: Welfare Foundation for Stem cell preservation methods technologies engineering TGF-β and other factors to control in vivo dif- therapeutic cloning nerve development in the artificial • SC from umbilical blood • Hair follicle SC Methods of collection, Cryopreservation Culturing in bioreactors and ferentiation towards cartilage rings Scientific Research Support organ • SC from the placental complex • Endometrium mesenchymal cells processing, and testing and thawing synthetic media • Dental pulp SC • Other types of SC (more invasive collec- Oocyte nuclear and citoplasm Transfer “science for Life Extension” tion procedures) firstname.lastname@example.org www.scienceagainstaging.com Remodelling enhancement, inflammation reduction and SC activation to propagate and to protect against Development of cell resourses ischemia (Boosting factors) Vascularization for therapeutic cloning Erythropoietin (Epo) as an “enhancing” factor in regeneration process Oocyte cryopreser- Human amniotic vation (oocyte bank, fluid SC immature oocytes) CELL REMOVAL Adding CELLs CELL REPROgRAMMing Cell sheets Study of iPSC as a unique subtype of pluripotent cell Reprogramming methods In vitro culturing Growth factors control Stem cell biomarkers hESC differentiation potential Identification of cancer stem cells Reduction of the number of anergic killer T-cells markers in various types of tumors Optimal growth-supporting microenvironment Morphological criteria of iPSC isolation for satellite cells Using hESC (somatic cell nuclear Organo-specific growth factors transfer, fusion with hESC) Specific markers of cellular (LGF, EGF, FGF, HGF, IGF, VEGF, Into hemopoetic Reduction of the amount surface BNDF, Epo, GCSF, GMCSF) or differentiated blood cells Population homogenity Markers CELLs fOR usE in tissuE EnginEERing of macrophages in visceral Gene expression signature and epigenetic remodeling of iPSC adipose tissues of senescent cells Differentiation and proliferation control Optimal combination Increasing reprogramming Without using hESC Molecular mechanisms of cancer Gene expression profiles in SC Via signalling pathways SC prolifera- Into insulin-producing beta cells of genetic factors efficiency (e.g. using kerati- stem cell population stability (JAK/STAT, MT-MMP, P19 ARF) tion control Expression regulation use of stem cells Possible markers of cells to remove of growth factors receptors for generation of nocytes for iPSC generation, study the sC properties of different origin therapeuticaly safe iPSC vitamin C) of various stage specificity • Telomerase reactivation, Necessary and sufficient Signaling mechanisms of self • Decreased levels of repair, factors to generate iPSC • Xenogenic • increase in oxidative DNA damage and inactivation of tumor Usage of targeted Creation of well-characterized ESC • ESC renewal and tumorigenesis Epigenetic pattern features Epigenetic control NfкB transcription factor • Allogeneiс supression. siRNA lines in cell banks • adult SC • Autologous Therapeutic applications of iPSC Using small molecules Therapy applications: Methods of cell removal Generation of patient-specific Obtaining a range of differ- In vivo cell growth features (disease-corrected) iPSC nent cell types from iPSC: Use of SC in repair of organ-tissue functions lost during aging • motoneurons, Apoptosis activation Differentiated hESC – for repair • cardiomyocytes, s Suicide gene therapy of the CNS integrity • mooth muscle cells, Therapy of diseases caused by locomotor (multiocular sclerosis, trauma) • endothelial cells, Using genes or gene sCAffOLd CREAtiOn fOR tissuE EnginEERing Therapy of age-related neurodegenerative diseases iPSC-based vaccination products Direct activation of proapoptotic New strategies in cell acquisition system aging • hematopoietic cells, Activation of proteins, “death receptors” and • primordial germ cells apoptosis though suppression of the apoptosis Elimination of cells signaling pathways Studies based on activation inhibitors activity • Parkinson’s desease of integration Bone tissue and Cells of vascular endothelium or Infertility treatment • Alzheimer’s desease MSC isolation Reprogramming of angiogenesis Enhancing the efficiency features for all articular cartilage their precursors – for treatment from adipose factors-delivery of induced • Multiocular sclerosis types of specialized cells using animal recovery using autologous MSC tissue of vascular network pathologies iPSC-based cellular systems: Decellularization pluripotent cells • ALSсклероз) Treatment of degenerative and animal models of tissues • non-integrating diseases: diseases: virus vectors, • Parkinson disease, Morphological evaluation Immune response stimulation • sickle cell aneamia, • polycistronic Vessel decellularization with minimal damage Rapid diagnostic technique of obtained grafts Dopaminergic neurons – • ALS etc. of cytoarchitectonic organization of grafts • familial dysautonomia, nonviral vectors, to the extracellular matrices using laser radiation for transplantation to patients utilizing laser-induced fluorescense SC isolation without viral Therapy of diseases associated with loss of myocardial function and tissue blood supply with Parkinson’s disease • spinal muscular atrophy, • adding recombi- Therapeutic humanized monoclonal Study of the mechanisms of tumor cell vectors and protooncogenes nant reprogram- • Down’s syndrome antibodies sustainability ming proteins Cell and gene therapies (CD133, VEGF, Treatment of genetic • Gaucher disease Cardiomyocyte FGF) for ischemia treatment: disorders: Reactivation of precursors • muscular dystrophies, hESC differentiation into • isickle cell anaemia, myocardial SC isolation from • lower limb atherosclerosis, neuroepithelium – for therapy • Parkinson’s disease, Identification of unwanted cells antigens Adaptive T-cell therapy Isolation of viable • diabetic foot, • Fanconi anaemia, pluripotent cells with nucleus hESC or iPSC of eye diseases • Huntington’s disease, from human donors • myocardial ischemia and others • hemophilia type A, • Duchenne muscular dystrophy • diabetes mellitus type I etc. Biomaterials natural biomaterials Use of urinary bladder matrix as a Marine sponges as precursors Fish scale in collagen scaffolds Biomaterials from silk protein and in the production of ceramic potential treatment for tympanic for corneal regeneration chitosan or gelatin for 3D scaffolds based tissue engineered bone membrane regeneration scaffolds REstORAtiOn Of REgEnERAtiVE POtEntiAL Chitosan Fibrin Optimization Microparticles from Effects of fibrino- Addressing the Hybrid stable STUDy of ExoGENoUS fACToRS oN REGENERATIvE PoTENTIAl of CEllS EPIGENETIC AlTERATIoNS DURING CHANGES IN ExTRACEllUlAR MATRIx chitosan with inorganic Fibrin scaffolds gen- and thrombin issue of using of photo- porous network with sustained release crosslinking REGENERATIoN components and MSC based fibrin gels for xenogenic from fibrinogen, of endothelial groth of fibrin gels to serve as bone-void neural tissue engi- stem cell in fibronectin and factor for greater fillers neering applications fibrin gels laminine Impact on cellular Uv-induced connective Beta-amyloid depositions stiffness Effects of P-selectin Non-enzymatically glycated Investigation microenvironment of • Protection of cells from oxidative stress Regulation of transcription in tissue regeneration, tissue aging products and other adhesion mol- of dedifferentiation SC niche to increase • Attraction of stem cells to the site of reparation also covalent modification of DNA and topological ecules on the aging rate mechanisms in vivo the repair potential • Stimulation of differentiation chromosome reorganisation for selective of SC manipulation of gene exprerssion Mechanisms of beta-amyloid deposits formation of SC Detection and quantification of non-enzymatically glycated proteins (AGE-products) Strategies for prevention of the extracellular matrix Mechanisms of the increase in levels and prophylaxis of photoaging Molecular mechanisms of the induction of metal ions in brain and other tissues synthetic biomaterials and progression of sporadic Alzheimer’s Activation of Notch signaling for vascular and their role information Mechanisms of maintaining the regenerative potential of SC populations through: disease regeneration with progenitor cells of beta-amyloid deposits Study of mechanisms of formation and regulation of AGE-products Reduction of toxicity of polyure- Biodegradable microspheres with Porous biocompatible cross-linked hydrogels Use of anti-inflammatory thane scaffolds linking components from organic Trophic factors Changes in basal membrane and Interaction with capillary endothelium compounds acid motifs and gelatin with poly- extracellular matrix parameters Genes governing (cyclooxygenase inhibitors, trimethylene carbonate in order to Modifying the polymeric sugar hyaluronic acid with varying regeneration of SC: inhibitors of cytokine Expression levels of a soluble form of the Prevention of beta-amyloid deposition construct porous scaffolds numbers of photocrosslinkable methacrylate groups in generation) AGE- products receptor as a biomarker of chronic Prosthetic vascular vessels for hydrogels for neural progenitor cell differentiation Biomaterials to direct Platelet-derived adhesin SDF-1 in situ arterial regeneration Mechanistic impact on SC stem-cell functions in differentiation of CD34+ into inflammatory diseases (vascular atherosclerosis, progenitor endothelial cells directing proliferation (e.g.,Plzf) diabetes, renal injury) Metal-chelators Porous ε-caprolactone membranes New agents to for nutrient supply and waste Self-assembled rosette Multilayered hydrogels destabilize and remove Porous polycaprolactone scaffolds product removal from the tissue nanotube/hydrogel com- with channels D-penicilamine- Lipophilic chelating preexisting amyloid and their construction using laser engineered construct posites for cartilage tissue for better distribution Secretion of cytokines and chemokines Anti-oxidant treatment Prevention of deposition of AGE-proteins deposits sintering Changes in intercellular contact parameters containing nanoparticles agent DP-109 for pre- engineering of oxygen and nutrients Secretion of non-protein substances IGF gene family encoding insulin- and removal of intermolecular protein-protein like growth factors crosslinks in treatment of vention of new amyloid Temporal patterns of neural Alzheimer’s disease, aggregates formation Microvesicule-vectored transfer Effects of nitric oxide (NO) on Parkinson’s disease, and and for solubilization Diopside (CaMgSi2O6) powders growth factor stimulation of genetic material between SC Protollin Electrospun nanofibrous scaffolds intracellular regeneration processes other central nervous of preexisting amyloid with biomimetic nanostructure and and dense ceramics as bioactive Porous fibrillar hyaluronic acid scaffolds Inhibition of matrix Generation of new glucose-lowering agents system disorders depots growth factors for control of SC biomaterials for bone repair using crystal templating Hox gene family encoding metalloproteases (MMP) behavior and fate transcription factors activity with: «Beta-sheet Adipose-derived hydro- • neutrophil elastase Clioquinol in treatment of Alzheimer’s disease breakers» Secretion of growth-stimulating factors (e.g. BMPs) Enzymatic crosslinking of gels for stimulation inhibitors, Hydroxyapatite particles/poly(ester- dextran-tyromine hydrogels of vascularized adipose Search for efficient inhibitors Multifunctional bioactive chemically • retinoids, urethane) with the advantage of an cross-linked elastin-like polymers formation in vivo encoding MAP kinases (pyridoxine, pyridoxamine, aminoguanidine, osteoconductive surface Regeneration processes in muscle tissue: • natural and synthetic 2,3-diamino phenazon, etc.) Proangiogenic effects inhibitors • Muscle-derived SC, mediated by the niche of exogenous erythropoietin Influence of various substances microenviroment Study of erythropoietin receptors on macrophages on homing of grafted cells • Non-muscle-derived SC in fibrin-unduced wound healing Therapeutics preventing interaction between amyloid deposition precursors • stimulatory and inhibitory growth factors responsible for cytoskeleton structure (e.g. lamin A) Development of synthetic drugs (2-phenyl- thiozoline, phenylsetam and its derivatives) Biomaterials quality protocols development using the criteria: and discovery of natural compounds Inhibitors of serum Natural compounds (wine-related polyphenols, Biological membranes Dissection of mechanisms amyloid P component tannic acid, curcumin, nicotine) STAT gene family encoding of photoinduced aging: Stiffness and stability Changes in physical parameters of intercellular environment No toxicity when biodegraded Biocompatibility with host tissue transcription activators at the site of implantation • functions and features of MMP, N-acetylcarnosine and histidyl Tissue engineered • mechanisms of photoinduction and hydrazide as promising therapeutics Inhibitors of the interaction between beta-amyloid fibers and beta-amyloid scaffolds based on natural Various oxygen tension values in tissue Influence of Са ions on osteoblast Influence of external electrical field on activation of MMP, for treatment of senile cataracts and pathological chaperons (ApoE, glucosaminglycans, etc.) bacterial membanes for modulation of regeneration processes differentiation for bone regeneration cytosceleton and membrain mechanics diabetic retinopathy Shape and size preservation of No rough encapsulation • specific and efficent MMP Minimal inflammation reconstructed organ р53/р21 gene axis or rejection of endoprosthesis inhibitors
"Regenerative Medicine Roadmap Poster"