scholarly journals Safety of Mesenchymal Stem Cells for Clinical Application

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Youwei Wang ◽  
Zhi-bo Han ◽  
Yong-ping Song ◽  
Zhong Chao Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Regenerative Medicine ◽  
Therapeutic Agents ◽  
Great Promise ◽  
Safety Issues ◽  
Human Use

Mesenchymal stem cells (MSCs) hold great promise as therapeutic agents in regenerative medicine and autoimmune diseases, based on their differentiation abilities and immunosuppressive properties. However, the therapeutic applications raise a series of questions about the safety of culture-expanded MSCs for human use. This paper summarized recent findings about safety issues of MSCs, in particular their genetic stability in long-termin vitroexpansion, their cryopreservation, banking, and the role of serum in the preparation of MSCs.

MYOGENIC DIFFERENTIATION OF HUMAN MESENCHYMAL STEM CELLS IN VITRO AND LONG-TERM SURVIVAL IN A NUDE RAT MODEL FOR URINARY INCONTINENCE

2009 ◽  
Vol 181 (4) ◽  
pp. 681
Author(s):  
Gerhard Feil ◽  
Adriana Drost ◽  
Simon Baumann ◽  
Jochen Schäfer ◽  
Sibylle Weng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Urinary Incontinence ◽  
Rat Model ◽  
Myogenic Differentiation ◽  
Human Mesenchymal Stem Cells ◽  
Term Survival ◽  
Nude Rat

scholarly journals DNA Methylation Changes duringIn VitroPropagation of Human Mesenchymal Stem Cells: Implications for Their Genomic Stability?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Angela Bentivegna ◽  
Mariarosaria Miloso ◽  
Gabriele Riva ◽  
Dana Foudah ◽  
Valentina Butta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Genomic Stability ◽  
Great Promise ◽  
Human Mscs ◽  
Low Oxygen ◽  
Long Term Culture ◽  
Functional Changes

Mesenchymal stem cells (MSCs) hold great promise for the treatment of numerous diseases. A major problem for MSC therapeutic use is represented by the very low amount of MSCs which can be isolated from different tissues; thusex vivoexpansion is indispensable. Long-term culture, however, is associated with extensive morphological and functional changes of MSCs. In addition, the concern that they may accumulate stochastic mutations which lead the risk of malignant transformation still remains. Overall, the genome of human MSCs (hMSCs) appears to be apparently stable throughout culture, though transient clonal aneuploidies have been detected. Particular attention should be given to the use of low-oxygen environment in order to increase the proliferative capacity of hMSCs, since data on the effect of hypoxic culture conditions on genomic stability are few and contradictory. Furthermore, specific and reproducible epigenetic changes were acquired by hMSCs duringex vivoexpansion, which may be connected and trigger all the biological changes observed. In this review we address current issues on long-term culture of hMSCs with a 360-degree view, starting from the genomic profiles and back, looking for an epigenetic interpretation of their genetic stability.

scholarly journals Soft Substrate Maintains Proliferative and Adipogenic Differentiation Potential of human Mesenchymal Stem Cells on Long Term Expansion by Delaying Senescence

2018 ◽  
Author(s):  
Sanjay K. Kureel ◽  
Pankaj Mogha ◽  
Akshada Khadpekar ◽  
Vardhman Kumar ◽  
Rohit Joshi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture System ◽  
Human Mesenchymal Stem Cells ◽  
Population Doubling ◽  
Differentiation Potential ◽  
Lineage Differentiation ◽  
Poly Acrylamide

AbstractHuman mesenchymal stem cells (hMSCs), when cultured on tissue culture plate (TCP) for in vitro expansion, they spontaneously lose their proliferative capacity and multi-lineage differentiation potential. They also lose their distinct spindle morphology and become large and flat. After a certain number of population doubling, they enter into permanent cell cycle arrest, called senescence. This is a major roadblock for clinical use of hMSCs which demands large number of cells. A cell culture system is needed which can maintain the stemness of hMSCs over long term passages yet simple to use. In this study, we explore the role of substrate rigidity in maintaining stemness. hMSCs were serially passaged on TCP and 5 kPa poly-acrylamide gel for 20 population doubling. It was found that while on TCP, cell growth reached a plateau at cumulative population doubling (CPD) = 12.5, on 5 kPa gel, they continue to proliferate linearly till we monitored (CPD = 20). We also found that while on TCP, late passage MSCs lost their adipogenic potential, the same was maintained on soft gel. Cell surface markers related to MSCs were also unaltered. We demonstrated that this maintenance of stemness was correlated with delay in onset of senescence, which was confirmed by β-gal assay and by differential expression of vimentin, Lamin A and Lamin B. As preparation of poly-acrylamide gel is a simple, well established, and well standardized protocol, we believe that this system of cell expansion will be useful in therapeutic and research applications of hMSCs.One Sentence SummaryhMSCs retain their stemness when expanded in vitro on soft polyacrylamide gel coated with collagen by delaying senescence.Significance StatementFor clinical applications, mesenchymal stem cells (MSCs) are required in large numbers. As MSCs are available only in scarcity in vivo, to fulfill the need, extensive in vitro expansion is unavoidable. However, on expansion, they lose their replicative and multi-lineage differentiation potential and become senescent. A culture system that can maintain MSC stemness on long-term expansion, without compromising the stemness, is need of the hour. In this paper, we identified polyacrylamide (PAA) hydrogel of optimum stiffness that can be used to maintain stemness of MSCs during in vitro long term culture. Large quantity of MSCs thus grown can be used in regenerative medicine, cell therapy, and in treatment of inflammatory diseases.

Effects Of Hypoxia in Long-Term In Vitro Expansion of Human Bone Marrow Derived Mesenchymal Stem Cells

2017 ◽  
Vol 118 (10) ◽  
pp. 3072-3079 ◽  
Author(s):  
Annelise Pezzi ◽  
Bruna Amorin ◽  
Álvaro Laureano ◽  
Vanessa Valim ◽  
Alice Dahmer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Bone ◽  
Human Bone Marrow ◽  
In Vitro Expansion

Abstract 5: Neovascularization By Substance-p- Mobilized Epc And Msc In Vitro And In Vivo

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hyun Sook Hong ◽  
Suna Kim ◽  
Youngsook Son
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Substance P ◽  
Network Formation ◽  
Skin Wound ◽  
Hematopoietic Stem ◽  
Vessel Structure

Bone marrow stem cells, especially, endothelial precursor cells (EPC), mesenchymal stem cells (MSC) or hematopoietic stem cell (HSC) are expected as reparative cells for the repair of a variety of tissue damages such as stroke and myocardial infarction, even though their role in the repair is not demonstrated. This report was investigated to find a role of Substance-p (SP) as a reparative agent in the tissue repair requiring EPC and MSC. In order to examine EPC (EPC SP ) and MSC (MSC SP ) mobilized by SP, we injected SP intravenously for consecutive 2 days and saline was injected as a vehicle. At 3 post injection, peripheral blood (PB) was collected.To get mesenchymal stem cells or endothelial progenitor cells, MNCs were incubated in MSCGM or EGM-2 respectively for 10 days. Functional characteristics of the EPC SP were proven by the capacity to form endothelial tubule network in the matrigel in vitro and in the matrigel plug assay in vivo. In contrast, MSC SP did not form a tube-like structure but formed a pellet-structure on matrigel. However, when both cells were premixed before the matrigel assay, much longer and branched tubular network was formed, in which a-SMA expressing MSC SP were decorating outside of the endothelial tube, especially enriched at the bifurcating point. MSC SP may contribute and reinforce elaborate vascular network formation in vivo by working as pericyte-like cells. Thus, the EPC SP and MSC SP were labeled with PKH green and PKH red respectively and their tubular network was examined. Well organized tubular network was formed, which was covered by PKH green labeled cells and was decorated in a punctate pattern by PKH red labeled cells. In order to investigate the role of EPC SP and MSC SP specifically in vivo, rabbit EPC SP and MSC SP were transplanted to full thickness skin wound. The vessel of EPC SP -transplanted groups was UEA-lectin+, which was not covered with a-SMA+ pericytes but EPC SP + MSC SP -transplanted groups showed, in part, a-SMA+ pericyte-encircled UEA-lectin+ vessels. This proved the specific role of MSC SP as pericytes. From these data, we have postulated that the collaboration of MSC and EPC is essential for normal vessel structure and furthermore, accelerated wound healing as ischemia diseases, which can be stimulated through by SP injection.

scholarly journals Insulin-Like Growth Factor Binding Protein-6 Promotes the Differentiation of Placental Mesenchymal Stem Cells into Skeletal Muscle Independent of Insulin-Like Growth Factor Receptor-1 and Insulin Receptor

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Doaa Aboalola ◽  
Victor K. M. Han
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Muscle Differentiation ◽  
Insulin Like Growth Factor ◽  
Differentiation Process ◽  
Placental Mesenchymal Stem Cells

As mesenchymal stem cells (MSCs) are being investigated for regenerative therapies to be used in the clinic, delineating the roles of the IGF system in MSC growth and differentiation, in vitro, is vital in developing these cellular therapies to treat degenerative diseases. Muscle differentiation is a multistep process, starting with commitment to the muscle lineage and ending with the formation of multinucleated fibers. Insulin-like growth factor binding protein-6 (IGFBP-6), relative to other IGFBPs, has high affinity for IGF-2. However, the role of IGFBP-6 in muscle development has not been clearly defined. Our previous studies showed that in vitro extracellular IGFBP-6 increased myogenesis in early stages and could enhance the muscle differentiation process in the absence of IGF-2. In this study, we identified the signal transduction mechanisms of IGFBP-6 on muscle differentiation by placental mesenchymal stem cells (PMSCs). We showed that muscle differentiation required activation of both AKT and MAPK pathways. Interestingly, we demonstrated that IGFBP-6 could compensate for IGF-2 loss and help enhance the muscle differentiation process by triggering predominantly the MAPK pathway independent of activating either IGF-1R or the insulin receptor (IR). These findings indicate the complex interactions between IGFBP-6 and IGFs in PMSC differentiation into the skeletal muscle and that the IGF signaling axis, specifically involving IGFBP-6, is important in muscle differentiation. Moreover, although the major role of IGFBP-6 is IGF-2 inhibition, it is not necessarily the case that IGFBP-6 is the main modulator of IGF-2.

scholarly journals Designing stem cell niches for differentiation and self-renewal

2018 ◽  
Vol 15 (145) ◽  
pp. 20180388 ◽  
Author(s):  
Hannah Donnelly ◽  
Manuel Salmeron-Sanchez ◽  
Matthew J. Dalby
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Regulatory Networks ◽  
Regulatory Mechanisms ◽  
Great Promise ◽  
Regenerative Capacity ◽  
Cell Niche ◽  
Stem Cell Niches

Mesenchymal stem cells, characterized by their ability to differentiate into skeletal tissues and self-renew, hold great promise for both regenerative medicine and novel therapeutic discovery. However, their regenerative capacity is retained only when in contact with their specialized microenvironment, termed the stem cell niche . Niches provide structural and functional cues that are both biochemical and biophysical, stem cells integrate this complex array of signals with intrinsic regulatory networks to meet physiological demands. Although, some of these regulatory mechanisms remain poorly understood or difficult to harness with traditional culture systems. Biomaterial strategies are being developed that aim to recapitulate stem cell niches, by engineering microenvironments with physiological-like niche properties that aim to elucidate stem cell-regulatory mechanisms, and to harness their regenerative capacity in vitro . In the future, engineered niches will prove important tools for both regenerative medicine and therapeutic discoveries.

191 Canine Mesenchymal Stem Cells as Therapeutic Agents in Spinal Cord Injured Dog

2018 ◽  
Vol 30 (1) ◽  
pp. 236 ◽  
Author(s):  
Y.-H. Choe ◽  
H.-J. Lee ◽  
S.-L. Lee ◽  
J.-H. Lee ◽  
B.-W. Park ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Agents ◽  
Clinical Applications ◽  
Pain Sensation ◽  
Differentiation Potential ◽  
Na Currents ◽  
Spinal Cord Injured

In the recent era of veterinary research, stem cells have gained special attention due to their efficiency and use in clinical applications. Mesenchymal stem cells (MSC) have been extensively studied over decades, and their prospect for clinical application is recognised in human medicine. Despite numerous reports in veterinary clinical trials of stem cells, few studies have been presented regarding the in vitro characterisation of canine mesenchymal stem cells (cMSC). Therefore, their efficacy as therapeutic agents in vitro has not been much elucidated. Canine adipose-derived mesenchymal stem cells (cAMSC) were characterised as per International Society for Cellular Therapy guidelines. Culturing cells showed spindle-like morphology and high proliferation rate. They displayed positive expression of mesenchymal markers CD44, CD90, and CD105, and lacked expression of CD34 and CD45. They were also positive for expression of pluripotency-related transcription factors (Oct3/4, Nanog, and Sox2) and showed differentiation potential towards mesodermal lineages. The cAMSC were further analysed for the neuronal trans-differentiation potential. Under appropriate differentiation conditions, cAMSC displayed distinctive dendritic morphology along with axon projections. Neuronal specific genes including Nestin, β-tubulin, neurofilament protein (NF-M, NF-H), and nerve growth factor (NGF) were also positively expressed. Nevertheless, functional analysis of neuronal differentiated cAMSC displayed voltage dependence and kinetics for transient K+ and Na+ currents (Ito). Both K+ and Na+ currents were recorded in differentiated MSC by voltage steps (between −120 and +60 mV for K+ currents, −40 and +50 mV for Na+ currents), whereas control undifferentiated MSC lacked the currents. Taken together, we concluded that the cAMSC have potential to differentiate into neuron-like cells. Based on these findings, we transplanted cAMSC into the spinal cord injured dogs to evaluate their clinical efficiency under approved medical guidelines set by Gyeongsang National University Animal Medical Center (Korea). Neurological examination showed that the injured dog had undergone hind limb paralysis and lost deep pain sensation due to an L2 spinal cord lesion, as detected by CT and MRI. The dog was diagnosed with traumatic L2 intradural spinal cord contusion, and decompression surgery was performed, but deep pain sensation did not recover. Therefore, each cAMSC (diluted in 0.5 mL of saline) was transplanted into spinal cord segment (L2~L3) 5 times at 1-week intervals. The dog showed mild recovery of deep pain sensation by neurological examinations and exhibited gradual improvement in hind limb function. Finally, we concluded that transplantation of cAMSC has a beneficial therapeutic effect on spinal cord injury. This study also provides a significant advantage in understanding the potential of MSC-based products in veterinary clinical applications.

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