385 Focal Enhanced Delivery of Systemically Administered Therapeutic Human Mesenchymal Stem Cells Using MRI-guided Disruption of the BBB with Focused Ultrasound

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 292-292
Author(s):  
Rawan Al-kharboosh ◽  
Nicholas Ellens ◽  
Katarina Cheng ◽  
Maarten Rotman ◽  
Jordan Green ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Focused Ultrasound ◽  
Cellular Therapy ◽  
Pulse Repetition Frequency ◽  
Human Mesenchymal Stem Cells ◽  
Brain Parenchyma ◽  
Brain Vasculature ◽  
First Time

Abstract INTRODUCTION Pre clinical interventions to the CNS require direct cranial administration of drugs for relevant therapeutic concentrations since the efficacy of systemic administration is hindered by the blood-brain barrier (BBB). We used MR-guided Focused Ultrasound (MRgFUS) to deliver primary-patient derived mesenchymal stem cells (hMSCs) for the first time, with sub-millimeter precision, in preselected areas. This method is a revolutionary way to deliver cellular therapy to delicate or inoperable regions obviating the need for invasive surgical intervention. METHODS MRgFUS mediates BBB opening when low intensity FUS is applied to brain vasculature containing circulating microbubbles. This causes high intensity oscillation leading to a pore formation in BBB. hMSCs were injected intracardially in mice as a proof-of-principal delivery system. Under guidance of MRI, 0.4-1MPa in situ pressures at 1 MHz, 1ms bursts and 1Hz pulse repetition frequency for 120 seconds were administered on the left hemisphere. Each animals contralateral brain served as its own control. RESULTS >We demonstrate that MRgFUS augments permeability of BBB. Each animal (n = 3) received 3 cavitation parameters ranging from .4-1MPa in situ pressures at time points 2, 6 and 24 hrs. Immunohistochemistry identified hMSC localization on sonicated points. Further analysis showed blood cell extravasation and capillary damage due to the indices being sonicated so close together causing a larger sheer force from the fluid stream of injected microbubbles. The consequence is a cavitation pore larger than intended, necessitating further optimization. There were no observed behavioral complications after sonication and no hMSCs localization in non-pulsed regions demonstrating precise localization and no off-target delivery. CONCLUSION The global hurdle of systemic therapy due to the BBB makes access of therapeutics, let alone cellular therapy to the brain parenchyma, nearly impossible. This study investigates for the first time the utility of FUS to non-destructively permeabilize the BBB by creating a transient pore big enough for hMSC access.

scholarly journals Transcriptome Profiling of IL-17A Preactivated Mesenchymal Stem Cells: A Comparative Study to Unmodified and IFN-γModified Mesenchymal Stem Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Kisha Nandini Sivanathan ◽  
Darling Rojas-Canales ◽  
Shane T. Grey ◽  
Stan Gronthos ◽  
Patrick T. Coates
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Antigen Processing ◽  
Cellular Therapy ◽  
Human Mesenchymal Stem Cells ◽  
Humoral Response ◽  
Transcriptome Profiling ◽  
Antigen Processing And Presentation ◽  
Immunomodulatory Function

Human mesenchymal stem cells pretreatment with IL-17A (MSC-17) potently enhances T cell immunosuppression but not their immunogenicity, in addition to avidly promoting the induction of suppressive regulatory T cells. The aim of this study was to identify potential mechanisms by which human MSC-17 mediate their superior immunomodulatory function. Untreated-MSC (UT-MSC), IFN-γtreated MSC (MSC-γ), and MSC-17 were assessed for their gene expression profile by microarray. Significantly regulated genes were identified for their biological functions (Database for Annotation, Visualisation and Integrated Discovery, DAVID). Microarray analyses identified 1278 differentially regulated genes between MSC-γand UT-MSC and 67 genes between MSC-17 and UT-MSC. MSC-γwere enriched for genes involved in immune response, antigen processing and presentation, humoral response, and complement activation, consistent with increased MSC-γimmunogenicity. MSC-17 genes were associated with chemotaxis response, which may be involved in T cell recruitment for MSC-17 immunosuppression. MMP1, MMP13, and CXCL6 were highly and specifically expressed in MSC-17, which was further validated by real-time PCR. Thus, MMPs and chemokines may play a key role in mediating MSC-17 superior immunomodulatory function. MSC-17 represent a potential cellular therapy to suppress immunological T cell responses mediated by expression of an array of immunoregulatory molecules.

scholarly journals STEM-03. FOCAL ENHANCED DELIVERY OF SYSTEMICALLY ADMINISTERED THERAPEUTIC HUMAN MESENCHYMAL STEM CELLS USING MRI-GUIDED DISRUPTION OF THE BBB WITH FOCUSED ULTRASOUND

2017 ◽  
Vol 19 (suppl_6) ◽  
pp. vi227-vi227
Author(s):  
Rawan Al-kharboosh ◽  
Nicholas Ellens ◽  
Katarina Cheng ◽  
Maarten Rotman ◽  
Jordan Green ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Focused Ultrasound ◽  
Human Mesenchymal Stem Cells ◽  
Mri Guided

scholarly journals The influence of the morphology of titania and hydroxyapatite on the proliferation and osteogenic differentiation of human mesenchymal stem cells

RSC Advances ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 3843-3853
Author(s):  
Yauheni U. Kuvyrkou ◽  
Nadzeya Brezhneva ◽  
Ekaterina V. Skorb ◽  
Sviatlana A. Ulasevich
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Osteogenic Potential ◽  
Titania Surface ◽  
Surface Modified ◽  
First Time ◽  
Ordered Porous ◽  
Porous Morphology

Herein, the proliferation and osteogenic potential of human mesenchymal stem cells (hMSCs) on the disordered and ordered porous morphology of the titania surface and titania surface modified by hydroxyapatite (HA) are compared for the first time.

scholarly journals Mesenchymal stem cells from amnion and amniotic fluid in the bovine

Reproduction ◽  
2013 ◽  
Vol 145 (4) ◽  
pp. 391-400 ◽  
Author(s):  
B Corradetti ◽  
A Meucci ◽  
D Bizzaro ◽  
F Cremonesi ◽  
A Lange Consiglio
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Amniotic Fluid ◽  
Cellular Therapy ◽  
Low Cost ◽  
Clinical Applications ◽  
Disease Treatment ◽  
First Time ◽  
Bovine Species ◽  
Proliferative Ability

Amnion and amniotic fluid (AF) are noncontroversial and inexhaustible sources of mesenchymal stem cells (MSCs) that can be harvested noninvasively at low cost. As in humans, also in veterinary field, presumptive stem cells derived from these tissues reveal as promising candidates for disease treatment, specifically for their plasticity, their reduced immunogenicity, and high anti-inflammatory potential. The aim of this work is to obtain and characterize, for the first time in bovine species, presumptive MSCs from the epithelial portion of the amnion (AECs) and from the AF (AF-MSCs) to be used for clinical applications. AECs display a polygonal morphology, whereas AF-MSCs exhibit a fibroblastic-like morphology only starting from the second passage, being heterogeneous during the primary culture. For both lines, the proliferative ability has been found constant over the ten passages studied and AECs show a statistically lower (P<0.05) doubling time with respect to AF-MSCs. AECs express MSC-specific markers (ITGB1(CD29),CD44,ALCAM(CD166),ENG(CD105), andNT5E(CD73)) from P1 to P3; in AF-MSCs, onlyITGB1,CD44, andALCAMmRNAs are detected;NT5Eis expressed from P2 andENGhas not been found at any passage. AF-MSCs and AECs are positive for the pluripotent markers (POU5F1(OCT4) andMYC(c-Myc)) and lack of the hematopoietic markers. When appropriately induced, both cell lines are capable of differentiating into ectodermal and mesodermal lineages. This study contributes to reinforce the emerging importance of these cells as ideal tools in veterinary medicine. A deeper evaluation of the immunological properties needs to be performed in order to better understand their role in cellular therapy.

scholarly journals Study of comparative proteome between normal and inverted karyotypes of human mesenchymal stem cells

2020 ◽  
Vol 42 ◽  
pp. e50260
Author(s):  
John Lenon De Souza Santos ◽  
Alice Barros Câmara ◽  
Isabella Tanus Job e Meira ◽  
Jonas Ivan Nobre Oliveira
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Genetic Instability ◽  
Cellular Therapy ◽  
Protein Profile ◽  
Cellular Stress ◽  
Human Mesenchymal Stem Cells ◽  
Mass Spectrometry Analysis

 Multipotent mesenchymal stem cells have been expanded in vitro for cellular therapy in numerous clinical settings without standardized culture conditions or quality-control schemes. The in vitro expansion is necessary to obtain sufficient cells for clinical applications. However, the expansion may induce genetic and functional abnormalities which may affect the safety and functionality of MSC, especially the chromosomal stability. This study aimed to investigate the protein profile of umbilical cord-derived MSC with normal and inverted karyotypes after expansion in the laboratory. Mass spectrometry analysis was performed and the Bradford method, Scaffold software, String and Cytoscape databases were employed to measure and characterize the protein content of umbilical cord-derived MSC. Networks of protein interactions, hub and bottleneck proteins were identified by proteomics and systems biology approaches. We found that proteins related to cellular stress were super expressed in inverted karyotype cells. Moreover, a high expression of Serpine 1, RHOA, and CTSB was found in these cells, which are proteins related to cancer. The albumin and ubiquitin proteins have been associated with a positive prognosis in cancer and cellular stress, and were up- and down-regulated in normal karyotype cells, respectively. The results suggests that the paracentric inversion inv(3)(p25p13) induced some type of cellular stress and genetic instability in human mesenchymal stem cells. These analyses showed the importance of carrying out studies related to the genetic instability of human mesenchymal stem cells using the protein expression profile as a parameter.

scholarly journals Characterization of Human Mesenchymal Stem Cells Isolated from the Testis

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Letizia De Chiara ◽  
Elvira Smeralda Famulari ◽  
Sharmila Fagoonee ◽  
Saskia K. M. van Daalen ◽  
Stefano Buttiglieri ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Human Mesenchymal Stem Cells ◽  
Spermatogonial Stem Cells ◽  
Great Promise ◽  
Human Testis ◽  
First Time

Mesenchymal stem cells hold great promise for regenerative medicine as they can be easily isolated from different sources such as adipose tissue, bone marrow, and umbilical cord blood. Spontaneously arising pluripotent stem cells can be obtained in culture from murine spermatogonial stem cells (SSCs), while the pluripotency of the human counterpart remains a matter of debate. Recent gene expression profiling studies have demonstrated that embryonic stem cell- (ESC-) like cells obtained from the human testis are indeed closer to mesenchymal stem cells (MSCs) than to pluripotent stem cells. Here, we confirm that colonies derived from human testicular cultures, with our isolation protocol, are of mesenchymal origin and do not arise from spermatogonial stem cells (SSCs). The testis, thus, provides an important and accessible source of MSCs (tMSCs) that can be potentially used for nephrotoxicity testing in vitro. We further demonstrate, for the first time, that tMSCs are able to secrete microvesicles that could possibly be applied to the treatment of various chronic diseases, such as those affecting the kidney.

scholarly journals Graphene Oxide Induced Osteogenesis Quantification by In-Situ 2D-Fluorescence Spectroscopy

2018 ◽  
Vol 19 (11) ◽  
pp. 3336 ◽  
Author(s):  
Valentina Palmieri ◽  
Marta Barba ◽  
Lorena Di Pietro ◽  
Claudio Conti ◽  
Marco De Spirito ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Graphene Oxide ◽  
Human Mesenchymal Stem Cells ◽  
Alizarin Red S ◽  
Alizarin Red ◽  
Tissue Sections ◽  
Osteogenic Induction ◽  
Calcium Deposits

Graphene and graphene oxide can promote the adhesion, growth and differentiation of mesenchymal stem cells. Further, graphene surface coatings accelerate the differentiation of human mesenchymal stem cells acting as osteogenic inducers. Quantification of the osteogenic induction is conventionally performed with Alizarin Red S (ARS), an anthraquinone derivative used to identify calcium deposits in tissue sections and cell cultures. The ARS staining is quite versatile because the dye forms an Alizarin Red S–calcium complex that can be extracted from the stained monolayer of cells and readily assayed by absorbance measurements. Direct visualization of stained deposits is also feasible; however, an in-situ visualization and quantification of deposits is possible only on transparent supports and not on thick opaque materials like ceramics and graphene composites that are well-known inducers of osteogenesis. In this manuscript, the shape of the 2D-fluorescence spectra of the ARS-calcium complex is used to develop a method to detect and monitor the in-situ differentiation process occurring during the osteogenic induction mediated by opaque graphene oxide surfaces.

Sign in / Sign up

Export Citation Format

Share Document