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Sharma, Hari Shanker
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Publications (10 of 213) Show all publications
Wiklund, L., Patnaik, R., Sharma, A., Miclescu, A. & Sharma, H. S. (2018). Cerebral Tissue Oxidative Ischemia-Reperfusion Injury in Connection with Experimental Cardiac Arrest and Cardiopulmonary Resuscitation: Effect of Mild Hypothermia and Methylene Blue. Molecular Neurobiology, 55(1), 115-121
Open this publication in new window or tab >>Cerebral Tissue Oxidative Ischemia-Reperfusion Injury in Connection with Experimental Cardiac Arrest and Cardiopulmonary Resuscitation: Effect of Mild Hypothermia and Methylene Blue
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 115-121Article in journal (Refereed) Epub ahead of print
Abstract [en]

The present investigation is an expansion of previous studies which all share a basic experimental protocol of a porcine-induced cardiac arrest (CA) of 12 min followed by 8 min of cardiopulmonary resuscitation (CPR), different experimental treatments (immediate as well as postponed induced mild hypothermia and administration of much or less cool intravenous fluids), and a follow-up period of 3 h after which the animals were sacrificed. Another group of animals was studied according to the same protocol after 12-min CA and Bstandard CPR.^ After death (within 1 min), the brains were harvested and frozen in liquid nitrogen awaiting analysis. Control brains of animals were collected in the same way after short periods of untreated CA (0 min, 5 min, and 15–30 min). Previous studies concerning chiefly neuropathological changes were now expanded with analyses of different tissue indicators (glutathione, luminol, leucigenin, malonialdehyde, and myeloperoxidase) of cerebral oxidative injury. The results indicate that a great part of oxidative injury occurs within the first 5 min after CA. Immediate cooling by administration of much intravenous fluid results in less cerebral oxidative injury compared to less intravenous fluid administration. A 30-min postponement of induction of hypothermia results in a cerebral oxidative injury comparable to that of Bstandard CPR^ or the oxidative injury found after 5 min of untreated CA. Intravenous administration of methylene blue (MB) during and immediately after CPR in combination with postponed cooling resulted in no statistical difference in any of the indicators of oxidative injury, except myeloperoxidase, and glutathione, when this treatment was compared with the negative controls, i.e., animals subjected to anesthesia alone.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Cardiac arrest, Oxidative injury, Ischemia reperfusion, Methylene blue
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-337384 (URN)10.1007/s12035-017-0723-z (DOI)000424702600012 ()28895060 (PubMedID)
Available from: 2017-12-24 Created: 2017-12-24 Last updated: 2018-04-04Bibliographically approved
Huang, H., Young, W., Chen, L., Feng, S., Al Zoubi, Z. M., Sharma, H. S., . . . Li, T. (2018). Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Cell Transplantation, 27(2), 310-324
Open this publication in new window or tab >>Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
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2018 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 27, no 2, p. 310-324Article, review/survey (Refereed) Published
Abstract [en]

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2018
Keywords
cell therapy, neurorestoration, clinical application guideline neurorestoratology
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-357188 (URN)10.1177/0963689717746999 (DOI)000430019200009 ()29637817 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Sharma, H. S., Muresanu, D. F., Vicente Lafuente, J., Patnaik, R., Tian, Z. R., Ozkizilcik, A., . . . Sharma, A. (2018). Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease. Molecular Neurobiology, 55(1), 300-311
Open this publication in new window or tab >>Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 300-311Article in journal (Refereed) Published
Abstract [en]

Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (A beta P), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of A beta P (1-40) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and A beta P concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (10(6) cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of A beta P infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 +/- 8 pg/g brain) along with a significant decrease in the A beta P deposition (45 pg/g from untreated control 75 pg/g; saline control 40 +/- 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Alzheimer's disease (AD), Neprilysin (NPL), Amyloid-beta peptide (a beta P), Mesenchymal stem cells (MSCs), Cerebrolysin (CBL), TiO2 nanowires, Nanodelivery
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346902 (URN)10.1007/s12035-017-0742-9 (DOI)000424702600030 ()28844104 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Sharma, A., Muresanu, D. F., Vicente Lafuente, J., Sjöquist, P.-O., Patnaik, R., Tian, Z. R., . . . Sharma, H. S. (2018). Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51. Molecular Neurobiology, 55(1), 276-285
Open this publication in new window or tab >>Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 276-285Article in journal (Refereed) Published
Abstract [en]

The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 degrees C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Traumatic brain injury (TBI), Oxidative stress, Luminol, Lucigenin, Malondialdehyde, Glutathione, H-290/51, Nanodelivery, Blood-brain barrier, Brain edema, Neuronal damage, Cold environment
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346900 (URN)10.1007/s12035-017-0740-y (DOI)000424702600028 ()28856566 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Sharma, H. S. & Sharma, A. (2018). Dedication Commendation of Diligence A Legend in Neuroscience (1948-2018) Dr. Stephen D. Skaper, Ph. D. CNS & Neurological Disorders: Drug Targets, 17(5), 322-322
Open this publication in new window or tab >>Dedication Commendation of Diligence A Legend in Neuroscience (1948-2018) Dr. Stephen D. Skaper, Ph. D
2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 5, p. 322-322Article in journal (Refereed) Published
Place, publisher, year, edition, pages
BENTHAM SCIENCE PUBL, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-365173 (URN)10.2174/187152731705180807144606 (DOI)000441416700002 ()
Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2018-11-09Bibliographically approved
Yang, H., Yang, Y., Qu, S., Wang, Z., Lu, W., Liu, F., . . . Luan, Z. (2018). Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation. CNS & Neurological Disorders: Drug Targets, 17(2), 98-105
Open this publication in new window or tab >>Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation
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2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 2, p. 98-105Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT.

Methods: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulin-like growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT.

Results: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without short-term therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05).

Conclusion: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.

Place, publisher, year, edition, pages
BENTHAM SCIENCE PUBL, 2018
Keywords
Mental retardation, neural precursor cell, transplantation, insulin-like growth factor 1, growth factors, intellectual disability
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-359677 (URN)10.2174/1871527317666180411102337 (DOI)000435906600004 ()29637872 (PubMedID)
Funder
Swedish Research Council, 2710
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-09-06Bibliographically approved
Patnaik, R., Sharma, A., Skaper, S. D., Muresanu, D. F., Vicente Lafuente, J., Castellani, R. J., . . . Sharma, H. S. (2018). Histamine H3 Inverse Agonist BF 2649 or Antagonist with Partial H4 Agonist Activity Clobenpropit Reduces Amyloid Beta Peptide-Induced Brain Pathology in Alzheimer's Disease. Molecular Neurobiology, 55(1), 312-321
Open this publication in new window or tab >>Histamine H3 Inverse Agonist BF 2649 or Antagonist with Partial H4 Agonist Activity Clobenpropit Reduces Amyloid Beta Peptide-Induced Brain Pathology in Alzheimer's Disease
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 312-321Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (A beta P) infusion-induced brain pathology in a rat model. AD-like pathology was produced by administering A beta P (1-40) intracerebroventricular (i.c.v.) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. Control rats received saline. In separate group of rats, either BF 2649 (1 mg/kg, i.p.) or clobenpropit (1 mg/kg, i.p.) was administered once daily for 1 week after 3weeks of A beta P administration. After 30 days, blood-brain barrier (BBB) breakdown, edema formation, neuronal, glial injuries, and A beta P deposits were examined in the brain. A significant reduction in A beta P deposits along with marked reduction in neuronal or glial reactions was seen in the drug-treated group. The BBB breakdown to Evans blue albumin and radioiodine in the cortex, hippocampus, hypothalamus, and cerebellum was also significantly reduced in these drug-treated groups. Clobenpropit showed superior effects than the BF2649 in reducing brain pathology in AD. Taken together, our observations are the first to show that blockade of H3 and stimulation of H4 receptors are beneficial for the treatment of AD pathology, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Alzheimer's disease (AD). Histamine. Amyloid beta peptide (A beta P), Clobenpropit, BF2649, H3 receptor inverse agonist, H3 receptors antagonist with partial H4 agonist, Blood-brain barrier, Brain pathology
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346903 (URN)10.1007/s12035-017-0743-8 (DOI)000424702600031 ()28861757 (PubMedID)
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
Milkina, E., Ponomarenko, A., Korneyko, M., Lyakhova, I., Zayats, Y., Zaitsev, S., . . . Bryukhovetskiy, I. (2018). Interaction of hematopoietic CD34(+) CD45(+) stem cells and cancer cells stimulated by TGF-beta 1 in a model of glioblastoma in vitro. Oncology Reports, 40(5), 2595-2607
Open this publication in new window or tab >>Interaction of hematopoietic CD34(+) CD45(+) stem cells and cancer cells stimulated by TGF-beta 1 in a model of glioblastoma in vitro
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2018 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 40, no 5, p. 2595-2607Article in journal (Refereed) Published
Abstract [en]

The majority of modern treatment methods for malignant brain tumors are not sufficiently effective, with a median survival time varying between 9 and 14 months. Metastatic and invasive processes are the principal characteristics of malignant tumors. The most important pathogenic mechanism is epithelial-mesenchymal transition (EMT), which causes epithelial cells to become more mobile, and capable of invading the surrounding tissues and migrating to distant organs. Transforming growth factor-beta 1 (TGF-beta 1) serves a key role in EMT-inducing mechanisms. The current study presented the interaction between hematopoietic stem cells and glioblastoma cells stimulated by TGF-beta 1 in vitro. The materials for the study were hematopoietic progenitor cell antigen CD34(+) hematopoietic stem cells (HSCs) and U87 glioblastoma cells. Cell culture methods, automated monitoring of cell-cell interactions, confocal laser microscopy, flow cytometry and electron microscopy were used. It was demonstrated that U87 cells have a complex communication system, including adhesive intercellular contacts, areas of interdigitation with dissolution of the cytoplasm, cell fusion, communication microtubes and microvesicles. TGF-beta 1 affected glioblastoma cells by modifying the cell shape and intensifying their exocrine function. HSCs migrated to glioblastoma cells, interacted with them and exchanged fluorescent tags. Stimulation of cancer cells with TGF-beta 1 weakened the ability of glioblastoma cells to attract HSCs and exchange a fluorescent tag. This process stimulated cancer cell proliferation, which is an indication of the ability of HSCs to 'switch' the proliferation and invasion processes in glioblastoma cells.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD, 2018
Keywords
glioblastoma, hematopoietic stem cells, transforming growth factor-beta 1, intercellular interaction
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-363198 (URN)10.3892/or.2018.6671 (DOI)000445341700017 ()30226551 (PubMedID)
Available from: 2018-10-19 Created: 2018-10-19 Last updated: 2018-10-19Bibliographically approved
Requejo, C., Ruiz-Ortega, J. A., Cepeda, H., Sharma, A., Sharma, H., Ozkizilcik, A., . . . Lafuente, J. V. (2018). Nanodelivery of Cerebrolysin and Rearing in Enriched Environment Induce Neuroprotective Effects in a Preclinical Rat Model of Parkinson's Disease. Molecular Neurobiology, 55(1), 286-299
Open this publication in new window or tab >>Nanodelivery of Cerebrolysin and Rearing in Enriched Environment Induce Neuroprotective Effects in a Preclinical Rat Model of Parkinson's Disease
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 286-299Article in journal (Refereed) Published
Abstract [en]

Rearing in enriched environment (EE) improves the recuperation in animal models of Parkinson's disease (PD). Administration of TiO2-nanowired cerebrolysin (CBL) could represent an additional strategy to protect or repair the nigrostriatal system. This study aims to explore morphofunctional and biochemical changes in a preclinical stage of PD testing the synergistic efficiency of combining both strategies, housing in EE, and nanodelivery of CBL. Sprague-Dawley male rats receiving intrastriatally 6-hydroxydopamine after a short evolution time were segregated into CBL group (rats receiving nanowired CBL), EE group (rats housed in EE), CBL + EE group (rats housed in EE and receiving nanowired CBL), and control group (rats without additional treatment). Prodromic stage and treatment effects were characterized by the presence of motor symptoms (amphetamine-induced rotational behavior test). Tyrosine hydroxylase (TH) immunohistochemistry and Western blot (p-Akt/Akt and p-ERK/ERK 1/2 as survival markers and caspase-3 as apoptotic marker) were performed in striatum and SN. A decrease in motor symptoms was shown by rats receiving CBL. EE monitoring cages revealed that rats from CBL + EE group showed more significant number of laps in the wheel than EE group. In SN, CBL + EE group also presented the highest neuronal density. Moreover, p-Akt/Akt and p-ERK/ERK 1/2 ratio was significant higher and caspase-3 expression was lower in CBL + EE group. In conclusion, the combination of CBL and EE provided evidence of neuoprotective-neurorestorative mechanisms by which this combined strategy promoted morphofunctional improvement by activation of survival pathways after dopamine depletion in a preclinical model of PD.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Parkinson'sdisease, 6-OHDA, Preclinical stage, Nanowired cerebrolysin, Enriched environment, Neuroprotection
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346901 (URN)10.1007/s12035-017-0741-x (DOI)000424702600029 ()28840482 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Bryukhovetskiy, I., Ponomarenko, A., Lyakhova, I., Zaitsev, S., Zayats, Y., Korneyko, M., . . . Khotimchenko, Y. (2018). Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review). International Journal of Molecular Medicine, 42(2), 691-702
Open this publication in new window or tab >>Personalized regulation of glioblastoma cancer stem cells based on biomedical technologies: From theory to experiment (Review)
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2018 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 42, no 2, p. 691-702Article, review/survey (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors. GBM represents >50% of primary tumors of the nervous system and similar to 20% of intracranial neoplasms. Standard treatment involves surgery, radiation and chemotherapy. However, the prognosis of GBM is usually poor, with a median survival of 15 months. Resistance of GBM to treatment can be explained by the presence of cancer stem cells (CSCs) among the GBM cell population. At present, there are no effective therapeutic strategies for the elimination of CSCs. The present review examined the nature of human GBM therapeutic resistance and attempted to systematize and put forward novel approaches for a personalized therapy of GBM that not only destroys tumor tissue, but also regulates cellular signaling and the morphogenetic properties of CSCs. The CSCs are considered to be an informationally accessible living system, and the CSC proteome should be used as a target for therapy directed at suppressing clonal selection mechanisms and CSC generation, destroying CSC hierarchy, and disrupting the interaction of CSCs with their microenvironment and extracellular matrix. These objectives can be achieved through the use of biomedical cellular products.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD, 2018
Keywords
glioblastoma multiforme, cancer stem cells, epithelial-mesenchymal transition, proteome, secretome, biomedical cellular product
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-366309 (URN)10.3892/ijmm.2018.3668 (DOI)000440581300001 ()29749540 (PubMedID)
Available from: 2018-11-20 Created: 2018-11-20 Last updated: 2018-11-20Bibliographically approved
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