Stem Cell Therapy and Its Products Such as Exosomes: Modern Regenerative Medicine Approach

Regenerative Medicine is a developing and multidisciplinary field of science that uses tissue engineering, biology, and cell or cell-free therapy to regenerate cells, tissues, and organs to restore their impaired or lost function. Regenerative medicine uses a new element linked to stem cells, which call exosomes, introduces it to the healthcare market. Exosomes are present in almost all body fluids, such as synovial fluid and blood. Exosomes and microvesicles are very efficient mediators of cell-to-cell communication by transferring their specific cargo to recipient cells. Furthermore, the modification of extracellular vesicles is possible that can become an excellent choice for drug delivery systems and vaccines. Isolation of exosomes for their use as therapeutic, research, or diagnostic agents for a specific type of disease is of particular importance. Five techniques have been used to isolate exosomes from different sources, including ultracentrifugation-based, size-based, immunoassay, exosome sedimentation, and microfluidic techniques. The use of exosomes in medicine has many applications, including in Bone and cartilage, dental, immune system, liver, kidney, skeletal muscle, nervous, heart systems, skin and wound, microbial and infectious, and also in cancers. This chapter focuses on stem cells, especially exosomes, as novel approaches in disease treatment and regenerative medicine

TIMPs Expression as A Maternal Cell Free Plasma Biomarker of Severe Preeclampsia: A Case-Control Study

Objective: Preeclampsia (PE) is a pregnancy related disorder with prevalence of 6-7%. Insufficient trophoblasticinvasion leads to incomplete remodeling of spiral arteries and consequent decrease in feto-placental perfusion. Alteredplacental expression of tissue inhibitors of matrix metalloproteinase (TIMPs) is considered to be involved in this processwhile the balance between matrix metalloproteinases (MMPs) and TIMPs contributes to remodeling of the placentaand uterine arteries by degradation and refurbishing of extracellular matrix (ECM). Therefore, TIMPs, fetal expressionpattern was evaluated with the aim of its potential to be used as a determinant for the (early) detection of PE. Materials and Methods: In this case-control study, cell free fetal RNA (cffRNA) released by placenta into the maternalblood was used to determine expression patterns of TIMP1, 2, 3 and 4 in the severe preeclamptic women in comparisonwith the normal pregnant women. Whole blood from 20 preeclamptic and 20 normal pregnant women in their 28-32weeks of gestational age was collected. The second control group consisted of 20 normal pregnant women in either 14or 28 weeks of gestation (each 10). cffRNA was extracted from plasma and real-time polymerase chain reaction (PCR)was done to determine the expression levels of TIMP1, 2, 3 and 4 genes. Results: Statistical analysis of the results showed significant higher expression of TIMP1-4 in the preeclamptic womenin comparison with the control group (P=0.029, 0.037, 0.037 and 0.049, respectively). Also, an increased level of TIMPsexpression was observed by comparing 14 to 28 weeks of gestational age in the normal pregnant women in the secondcontrol group. Conclusion: An increased cffRNA expression level of TIMPs may be correlated with the intensity of placental vasculardefect and may be used as a determinant of complicated pregnancies with severe preeclampsia

Nanomechanotransduction of human mesenchymal stem cells an application of medical nanobiotechnology

In this project the influences on human adult mesenchymal stem cells using nanomechanical stimulation techniques has been explored. It is expected that human mesenchymal stem cells will find use in many autologous regenerative therapies and in tissue engineering. However, the ability to control stem cell growth and differentiation is presently limited, and this is a major hurdle to the clinical use of these multipotent cells especially when considering the desire not to use soluble factors or complex media formulations in culture. Also, unpredictable number of cells required to be clinically useful is currently a hurdle to using materials-based (stiffness, chemistry, nanotopography, etc.) culture substrates. According to known cellular reactions to environmental stimuli, it was expected that human cells show some reactions to nanoscale vibration that in the case of stem cells it could be a differentiation response. This thesis gives a first demonstration of using nanoscale mechanotransductive protocols (10-14 nm vertical displacements at 1 kHz frequency), “nanokicking”, to promote osteoblastogenesis in human mesenchymal stem cell cultures. On the basis of application of the reverse piezo effect, laser interferometry was used to develop the optimal stem cell stimulation conditions, allowing delivery of nanoscale cues across the entire surface of the Petri dishes used. A combination of biological techniques has then been used to demonstrate osteoblastogenesis. Furthermore, RhoA has been implicated as being central to osteoblastic differentiation in agreement with materials-based strategies. We validate this with pharmacological inhibition of RhoA kinase. It is easy to envisage such stimulation protocols being up-scaled to form large-scale osteoblast bioreactors as standard cell culture plates and incubators are used in the protocol

A review on tissue engineering scaffolds and their function in regenerative medicine

 One of the challenges that medical sciences has long been facing is to find the best therapeutic method for the damaged tissues. The main purpose of tissue engineering and regenerative medicine is the development of biological implant or engineered tissues to repair, regenerate or replace the damaged tissue and maintain the organ function. At the moment, a lot of research has been done in the field of nanotechnology on the application of nanomaterials in medicine, because the surface of these nanomaterials increases with decreasing their size with change or increases in effect concommitantly. In recent decades, the production of medical textiles (Including nano fibers) has been provided good services to the regenerative medicine. In the field of biomedical applications, it is often necessary to combine biological and medical sciences with materials science and engineering. One of the most important application of tissue engineering is the usage of nanofiber matrix as scaffolds for the cell growth and proliferation. In this paper, various types of engineered scaffolds and their functions have been presented and evaluated. &nbsp

A smart magnetic hydrogel containing exosome promotes osteogenic commitment of human adipose-derived mesenchymal stem cells

OBJECTIVE(S): Exosomes, as nano-sized extracellular vehicles acting as cell-to-cell communicators, are novel promising therapeutics in the area of bone tissue engineering. Moreover, magnetic nanoparticles, whose integration with other appropriate components is viewed as an intriguing approach to strengthen bone tissue engineering efficacy. We investigated the effect of magnetic enriched with exosomes on osteogenic differentiation. MATERIALS AND METHODS: Exosomes were isolated from human adipose-derived mesenchymal stem cells by Exo-spin™ kit (MSC-EX). Alginate (Alg) scaffold containing 1% (w/w) cobalt ferrite nanoparticles (CoFe2O4) was produced. MSC-EX were gently loaded onto Alg and Alg-cobalt ferrite (Alg-CF) scaffolds yielding Alg-EX and Alg-CF-EX scaffolds. The effects of MSC-Ex and magnetic hydrogel composite under an external static magnetic field (SMF) on proliferation and differentiation of MSCs were evaluated by alkaline phosphatase (ALP) activity measurement, alizarin red staining, and energy dispersive X-ray (EDX) analysis. RESULTS: Our results showed that Alg and Alg-CF scaffolds were not only cytotoxic but also supported AdMSCs proliferation. MSC-EX loading of the scaffolds enhanced AdMSCs proliferation significantly. According to the results, Alg-CF-EX scaffolds under magnetic stimulation exhibited the most potent effect on osteogenic differentiation of cultured AdMSCs as evidenced by higher ALP activity and mineralization. CONCLUSION: We provided evidence that the combination of Alg hydrogel, CFNPs, and MSC-EX resulted in the construction of a bone tissue-engineering scaffold that highly supports the osteogenic commitment of MSCs

Production of nanoscale vibration for stimulation of human mesenchymal stem cells

Mechanical stimulation is becoming a common technique for manipulating cell behaviour in bioengineering with applications in tissue engineering and possibly regenerative therapy. Living organisms show biological responses in vivo and in vitro to various types of mechanical stimulation including vibration. The development of apparatus to produce vertical motions of nanoscale amplitude is detailed and their effect on mouse endothelial (Le2) and human mesenchymal stem cells (hMSCs) is investigated. Piezo ceramic actuators and aluminium reinforcement were utilised along with laser interferometry to ensure amplitude consistency at the nanometre level across a cell culture substrate. Peak force applied to the cells was estimated to be of nN magnitude at frequencies of 500 and 1000 Hz. Morphological changes in the cytoskeleton were found for both cell types along with increased MSC proliferation after 1 week of stimulation at 500 Hz. Changes in the nuclear size of MSCs after stimulation were also found

Human embryonic stem cells and good manufacturing practice: Report of a 1- day workshop held at Stem Cell Biology Research Center, Yazd, 27th April 2017

This report explains briefly the minutes of a 1-day workshop entitled; “human embryonic stem cells (hESCs) and good manufacturing practice (GMP)” held by Stem Cell Biology Research Center based in Yazd Reproductive Sciences Institute at Shahid Sadoughi University of Medical Sciences, Yazd, Iran on 27th April 2017. In this workshop, in addition to the practical sessions, Prof. Harry D. Moore from Centre for Stem Cell Biology, University of Sheffield, UK presented the challenges and the importance of the biotechnology of clinical-grade human embryonic stem cells from first derivation to robust defined culture for therapeutic applications

Ecology and postmodernity

Includes bibliographical referencesAvailable from British Library Document Supply Centre- DSC:DX220497 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Nanoscale stimulation of osteoblastogenesis from mesenchymal stem cells: nanotopography and nanokicking

AIM: Mesenchymal stem cells (MSCs) have large regenerative potential to replace damaged cells from several tissues along the mesodermal lineage. The potency of these cells promises to change the longer term prognosis for many degenerative conditions currently suffered by our aging population. We have endeavored to demonstrate our ability to induce osteoblatogenesis in MSCs using high-frequency (1000-5000 Hz) piezo-driven nanodisplacements (16-30 nm displacements) in a vertical direction. <p></p> MATERIALS and METHODS: Osteoblastogenesis has been determined by the upregulation of osteoblasic genes such as osteonectin (ONN), RUNX2 and Osterix, assessed via quantitative real-time PCR; the increase of osteocalcin (OCN) and osteopontin (OPN) at the protein level and the deposition of calcium phosphate determined by histological staining.<p></p> RESULTS: Intriguingly, we have observed a relationship between nanotopography and piezo-stimulated mechanotransduction and possibly see evidence of two differing osteogenic mechanisms at work. These data provide confidence in nanomechanotransduction for stem cell differentiation without dependence on soluble factors and complex chemistries.<p></p> CONCLUSION: In the future it is envisaged that this technology may have beneficial therapeutic applications in the healthcare industry, for conditions whose overall phenotype maybe characterized by weak or damaged bones (e.g., osteoporosis and bone fractures), and which can benefit from having an increased number of osteoblastic cells in vivo.<p></p&gt