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Stem Cells Dev. 2013 May 15. [Epub ahead of print]
Mesenchymal stromal cell characteristics vary depending on their origin.
Wegmeyer H, Broeske AM, Leddin M, Kuentzer K, Nisslbeck AK, Hupfeld J, Wiechmann K, Kuhlen J, von
Schwerin C, Stein C, Knothe S, Funk J, Huss R, Neubauer M.
Source
Roche Diagnostics GmbH, pharma Research and Early Development (pRED), Penzberg, Germany ;
[email protected].
Abstract
Mesenchymal stromal cells (MSCs) are rare progenitor cells that can be isolated from various tissues. They
exhibit multilineage differentiation potential, support regenerative processes, and interact with various
immune cells. Therefore, MSCs represent a promising tool for regenerative medicine. However, sourcedependent and donor-dependent differences of MSC properties including implications on their clinical
application are still largely unknown. We evaluated MSCs derived from perinatal tissues umbilical cord (UC)
and amniotic membrane (AM) in comparison to adult MSCs from bone marrow (BM) which were used as
gold standard. We found genetic background-independent differences between MSCs from UC and AM.
While AM- and UC-MSCs were closer to each other than to BM-MSCs, however, they also exhibited
differences between each other. AM-MSCs from different donors but not UC-MSCs displayed high interdonor variability. In addition, we show that although all MSCs expressed similar surface markers, MSC
populations from UC and AM showed differential profiles of gene expression and paracrine factor secretion
to BM-derived MSCs. Notably, pathway analysis of gene expression data revealed intriguing differences
between MSCs suggesting that MSCs from UC and AM possess in general a higher potential of
immunomodulatory capacity whereas BM-MSCs showed a higher potential of supporting regenerative
processes as exemplified by neuronal differentiation and development. These differences between perinatal
and BM-derived MSCs may be relevant for clinical applications.
Stem Cell Res Ther. 2013 Apr 29;4(2):42. [Epub ahead of print]
The dual role of mesenchymal stem cells in tumor progression.
Gomes CM.
Source
Laboratory of Pharmacology and Experimental Therapeutics, IBILI - Faculty of Medicine, University of
Coimbra, Portugal, Azinhaga de Sta Comba - Celas, Coimbra, 3000-548, Portugal. [email protected].
Abstract
Mesenchymal stem cells (MSCs) have attracted increasing interest in the field of oncology because of their
inherent capacity to migrate and home tumor tissues. The remarkable tropism of MSCs for tumor
microenvironments has been exploited in order to use these cells as cellular vehicles to deliver gene
therapies or anticancer agents. At functional levels, these cells display chemotactic properties similar to
those of immune cells in response to tissue insult and inflammation and secrete a broad range of bioactive
biomolecules with an impact on tumor development and a progression through direct actions on tumor cells
and the stromal microenvironment. However, the exact contribution of such interactions in tumor progression
has not yet been fully clarified, and some concerns remain regarding whether MSCs exert a tumorsuppressive effect or, on the contrary, favor tumor growth.
Tissue Eng Part B Rev. 2013 May 16. [Epub ahead of print]
Skeletal Muscle Tissue Engineering: Which Cell to Use?
Fishman JM, Tyraskis A, Maghsoudlou P, Urbani L, Totonelli G, Birchall M, De Coppi P.
Source
UCL Institute of Child Health, Surgery Department, 30 Guilford Street, London, United Kingdom, WC1N 1EH,
+447989331573 ; [email protected].
Abstract
Tissue-engineered skeletal muscle is urgently required to treat a wide array of devastating congenital and
acquired conditions. Selection of the appropriate cell type requires consideration of several factors which
amongst others include, accessibility of the cell source, in vitro myogenicity at high efficiency with the ability
to maintain differentiation over extended periods of time, susceptibility to genetic manipulation, a suitable
mode of delivery and finally in vivo differentiation giving rise to restoration of structural morphology and
function. Potential stem-progenitor cell sources include and are not limited to satellite cells, myoblasts,
mesoangioblasts, pericytes, muscle side-population cells, CD133+ cells, in addition to embryonic stem cells,
mesenchymal stem cells, amniotic fluid stem cells and induced pluripotent stem cells. The relative merits and
inherent limitations of these cell types within the field of tissue-engineering are discussed in the light of
current research. Recent advances in the field of induced pluripotent stem cells should bear the fruits for
some exciting developments within the field in the forthcoming years
Mol Cells. 2013 May 14. [Epub ahead of print]
Phenotypic characterization and in vivo localization of human adipose-derived mesenchymal stem
cells.
Ryu YJ, Cho TJ, Lee DS, Choi JY, Cho J.
Source
Department of Pathology, College of medicine, Kangwon National University, Chuncheon, 200-701, Korea.
Abstract
Human adipose-derived mesenchymal stem cells (hADMSCs) are a potential cell source for autologous cell
therapy due to their regenerative ability. However, detailed cytological or phenotypic characteristics of these
cells are still unclear. Therefore, we determined and compared cell size, morphology, ultrastructure, and
immunohistochemical (IHC) expression profiles of isolated hADMSCs and cells located in human adipose
tissues. We also characterized the localization of these cells in vivo. Light microscopy examination at low
power revealed that hADMSCs acquired a spindle-shaped morphology after four passages. Additionally,
high power views showed that these cells had various sizes, nuclear contours, and cytoplasmic textures. To
further evaluate cell morphology, transmission electron microscopy was performed. hADMSCs typically had
ultrastructural characteristics similar to those of primitive mesenchymal cells including a relatively high
nuclear/cytosol ratio, prominent nucleoli, immature cytoplasmic organelles, and numerous filipodia. Some
cells contained various numbers of lamellar bodies and lipid droplets. IHC staining demonstrated that
PDGFR and CD10 were constitutively expressed in most hADMSCs regardless of passage number but
expression levels of α-SMA, CD68, Oct4 and c-kit varied. IHC staining of adipose tissue showed that cells
with immunophenotypic characteristics identical to those of hADMSCs were located mainly in the
perivascular adventitia not in smooth muscle area. In summary, hADMSCs were found to represent a
heterogeneous cell population with primitive mesenchymal cells that were mainly found in the perivascular
adventitia. Furthermore, the cell surface markers would be CD10/PDGFR. To obtain defined cell populations
for therapeutic purposes, further studies will be required to establish more specific isolation methods.
Biotechnol Prog. 2013 May 15. doi: 10.1002/btpr.1747. [Epub ahead of print]
Comparative analysis of reference gene stability in human mesenchymal stromal cells during
osteogenic differentiation.
Jacobi A, Rauh J, Bernstein P, Liebers C, Zou X, Stiehler M.
Source
Dept. of Orthopaedics and Centre for Translational Bone, Joint and Soft Tissue Research, University
Hospital Carl Gustav Carus, 01307, Dresden, Germany.
Abstract
Mesenchymal stromal cells (MSCs) are one of the most frequently used cell sources for tissue engineering
strategies. Cultivation of osteogenic MSCs is a prerequisite for cell-based concepts that aim at bone
regeneration. Quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) analysis is a
commonly used method for the examination of mRNA expression levels. However, data on suitable
reference genes for osteogenically cultivated MSCs is scarce. Hence, the aim of the study was to compare
the regulation of different potential reference genes in osteogenically stimulated MSCs. Human MSCs were
isolated from bone marrow aspirates of N = 6 hematologically healthy individuals, expanded by polystyreneadherence, and maintained with and without osteogenic supplements for 14 days. Cellular proliferation and
osteogenic differentiation were assessed by total DNA quantification, cell-specific alkaline phosphatase
(ALP) activity and by qualitative staining for ALP and alizarin red, respectively. mRNA expression levels of N
= 32 potential reference genes were quantified using the human Endogenous Control TaqMan® assays.
mRNA expression stability was calculated using geNorm. The combined use of the most stable reference
genes and DNA-damage-inducible alpha, Pumilio homolog 1, and large ribosomal protein P0 significantly
improved gene expression accuracy as compared to the use of the commonly used reference genes beta
actin and glyceraldehyde-3-phosphate dehydrogenase during qRT-PCR-based target gene expression
analysis of osteogenically stimulated MSCs
Stem Cell Res Ther. 2013 May 14;4(3):47. [Epub ahead of print]
Age-associated changes in the ecological niche: implications for mesenchymal stem cell aging.
Asumda FZ.
Source
Saint James School of Medicine, 1480 Renaissance Drive, Park Ridge, Chicago, IL, 60068, USA.
[email protected].
Abstract
Adult stem cells are critical for organ-specific regeneration and self-renewal with advancing age. The
prospect of being able to reverse tissue-specific post-injury sequelae by harvesting, culturing and
transplanting a patient's own stem and progenitor cells is exciting. Mesenchymal stem cells have emerged
as a reliable stem cell source for this treatment modality and are currently being tested in numerous ongoing
clinical trials. Unfortunately, the fervor over mesenchymal stem cells is mitigated by several lines of evidence
suggesting that their efficacy is limited by natural aging. This article discusses the mechanisms and
manifestations of age-associated deficiencies in mesenchymal stem cell efficacy. A consideration of recent
experimental findings suggests that the ecological niche might be responsible for mesenchymal stem cell
aging.
J Cell Mol Med. 2013 May 15. doi: 10.1111/jcmm.12061. [Epub ahead of print]
Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation.
Wang YK, Chen CS.
Source
Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei,
Taiwan; Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
Abstract
Stem cells have been shown to have the potential to provide a source of cells for applications to tissue
engineering and organ repair. The mechanisms that regulate stem cell fate, however, mostly remain unclear.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that are isolated from bone marrow and
other adult tissues, and can be differentiated into multiple cell lineages, such as bone, cartilage, fat, muscles
and neurons. Although previous studies have focused intensively on the effects of chemical signals that
regulate MSC commitment, the effects of physical/mechanical cues of the microenvironment on MSC fate
determination have long been neglected. However, several studies provided evidence that mechanical
signals, both direct and indirect, played important roles in regulating a stem cell fate. In this review, we
summarize a number of recent studies on how cell adhesion and mechanical cues influence the
differentiation of MSCs into specific lineages. Understanding how chemical and mechanical cues in the
microenvironment orchestrate stem cell differentiation may provide new insights into ways to improve our
techniques in cell therapy and organ repair.
Am J Stem Cells. 2013 Mar 8;2(1):62-73. Print 2013.
Effect of extracorporeal shock wave on proliferation and differentiation of equine adipose tissue-derived
mesenchymal stem cells in vitro.
Raabe O, Shell K, Goessl A, Crispens C, Delhasse Y, Eva A, Scheiner-Bobis G, Wenisch S, Arnhold S.
Source
Institute of Veterinary -Anatomy, -Histology, and -Embryology, Justus-Liebig University of Giessen Germany.
Abstract
Mesenchymal stem cells are regarded as common cellular precursors of the musculoskeletal tissue and are responsible
for tissue regeneration in the course of musculoskeletal disorders. In equine veterinary medicine extracorporeal shock
wave therapy (ESWT) is used to optimize healing processes of bone, tendon and cartilage. Nevertheless, little is known
about the effects of the shock waves on cells and tissues. Thus, the aim of this study was to investigate the influence of
focused ESWT on the viability, proliferation, and differentiation capacity of adipose tissue-derived mesenchymal stem
cells (ASCs) and to explore its effects on gap junctional communication and the activation of signalling cascades
associated with cell proliferation and differentiation. ASCs were treated with different pulses of focused ESWT. Treated
cells showed increased proliferation and expression of Cx43, as detected by means of qRT-PCR, histological staining,
immunocytochemistry and western blot. At the same time, cells responded to ESWT by significant activation
(phosphorylation) of Erk1/2, detected in western blots. No significant effects on the differentiation potential of the
ASCs were evident. Taken together, the present results show significant effects of shock waves on stem cells in vitro.
Am J Stem Cells. 2013 Mar 8;2(1):22-38. Print 2013.
Mesenchymal stem cell and regenerative medicine: regeneration versus immunomodulatory challenges.
Law S, Chaudhuri S.
Source
Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of
Tropical Medicine 108 C R Avenue, Kolkata-700073, India.
Abstract
Mesenchymal Stem cells (MSC) are now presented with the opportunities of multifunctional therapeutic approaches.
Several reports are in support of their self-renewal, capacity for multipotent differentiation, and immunomodulatory
properties. They are unique to contribute to the regeneration of mesenchymal tissues such as bone, cartilage, muscle,
ligament, tendon, and adipose. In addition to promising trials in regenerative medicine, such as in the treatment of major
bone defects and myocardial infarction, MSC has shown a therapeutic effect other than direct hematopoiesis support in
hematopoietic reconstruction. MSCs are identified by the expression of many molecules including CD105 (SH2) and
CD73(SH3/4) and are negative for the hematopoietic markers CD34, CD45, and CD14. Manufacturing of MSC for
clinical trials is also an important aspect as their differentiation, homing and Immunomodulatory properties may differ.
Their suppressive effects on immune cells, including T cells, B cells, NK cells and DC cells, suggest MSCs as a novel
therapy for GVHD and other autoimmune disorders. Since the cells by themselves are non-immunogenic, tissue
matching between MSC donor and recipient is not essential and, MSC may be the first cell type able to be used as an
"off-the-shelf" therapeutic product. Following a successful transplantation, the migration of MSC to the site of injury
refers to the involvement of chemokines and chemokine receptors of respective specificity. It has been demonstrated
that cultured MSCs have the ability to engraft into healthy as well as injured tissue and can differentiate into several cell
types in vivo, which facilitates MSC to be an ideal tool for regenerative therapy in different disease types. However,
some observations have raised questions about the limitations for proper use of MSC considering some critical factors
that warn regular clinical use.
Curr Opin Gastroenterol. 2013 May 9. [Epub ahead of print]
Stem cell therapy in inflammatory bowel disease: which, when and how?
van Deen WK, Oikonomopoulos A, Hommes DW.
Source
aDepartment of Digestive Diseases, David Geffen School of Medicine, UCLA, Los Angeles, California, USA
bDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The
Netherlands.
Abstract
PURPOSE OF REVIEW:
Stem cell therapy has emerged as a promising therapeutic strategy for inflammatory bowel diseases (IBDs).
Currently, stem cell therapy is not part of the standard of care and is usually only performed as a part of
clinical trials. In this review, clinical results, proposed underlying mechanisms, and future research directions
will be discussed.
RECENT FINDINGS:
Administration of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) has been evaluated
for IBD treatment over the past years. MSC therapy is being explored as a treatment option for fistulizing
Crohn's disease and for luminal Crohn's disease. It is shown to be well tolerated, but results on efficacy are
inconsistent. HSC transplantation seems to be very effective, but serious adverse events are common.
Therefore, future research should focus on improving efficacy of MSC therapy, and on improvement of safety
of HSC therapy.
SUMMARY:
Both MSC and HSC therapy offer clinical potential, but currently are not routinely used for IBD treatment.
MSC therapy seems well tolerated but results on efficacy are conflicting. HSC transplantation is shown to be
effective but safety concerns remain. Nonetheless, for severe refractory IBD cases, stem cell therapy could
well become the next-generation treatment option.
Biotechnol Prog. 2013 May 15. doi: 10.1002/btpr.1747. [Epub ahead of print]
Comparative analysis of reference gene stability in human mesenchymal stromal cells during
osteogenic differentiation.
Jacobi A, Rauh J, Bernstein P, Liebers C, Zou X, Stiehler M.
Source
Dept. of Orthopaedics and Centre for Translational Bone, Joint and Soft Tissue Research, University
Hospital Carl Gustav Carus, 01307, Dresden, Germany.
Abstract
Mesenchymal stromal cells (MSCs) are one of the most frequently used cell sources for tissue engineering
strategies. Cultivation of osteogenic MSCs is a prerequisite for cell-based concepts that aim at bone
regeneration. Quantitative real time reverse transcription polymerase chain reaction (qRT-PCR) analysis is a
commonly used method for the examination of mRNA expression levels. However, data on suitable
reference genes for osteogenically cultivated MSCs is scarce. Hence, the aim of the study was to compare
the regulation of different potential reference genes in osteogenically stimulated MSCs. Human MSCs were
isolated from bone marrow aspirates of N = 6 hematologically healthy individuals, expanded by polystyreneadherence, and maintained with and without osteogenic supplements for 14 days. Cellular proliferation and
osteogenic differentiation were assessed by total DNA quantification, cell-specific alkaline phosphatase
(ALP) activity and by qualitative staining for ALP and alizarin red, respectively. mRNA expression levels of N
= 32 potential reference genes were quantified using the human Endogenous Control TaqMan® assays.
mRNA expression stability was calculated using geNorm. The combined use of the most stable reference
genes and DNA-damage-inducible alpha, Pumilio homolog 1, and large ribosomal protein P0 significantly
improved gene expression accuracy as compared to the use of the commonly used reference genes beta
actin and glyceraldehyde-3-phosphate dehydrogenase during qRT-PCR-based target gene expression
analysis of osteogenically stimulated MSCs.
Stem Cells. 2013 May 16. doi: 10.1002/stem.1400. [Epub ahead of print]
Two Negative Feedback Loops Place Mesenchymal Stem/Stromal Cells (MSCs) at the Center of Early
Regulators of Inflammation.
Prockop DJ.
Source
Texas A&M Health Science Center College of Medicine Institute for Regenerative Medicine at Scott & White,
Module C, 5701 Airport Road, Temple, TX 76502, USA. [email protected].
Abstract
Recent data demonstrated that MSCs can be activated by pro-inflammatory signals to introduce two
negative feedback loops into the generic pathway of inflammation. In one loop, the activated MSCs secrete
PGE2 that drives resident macrophages with an M1 pro-inflammatory phenotype toward an M2 antiinflammatory phenotype. In the second loop, the activated MSCs secrete TSG-6 that interacts with CD44 on
resident macrophages to decrease TLR2/NFκ-B signaling and thereby decrease the secretion of proinflammatory mediators of inflammation. The PGE2 and TSG-6 negative feedback loops allow MSCs to
serve as regulators of the very early phases of inflammation. These and many related observations suggest
that the MSC-like cells found in most tissues may be part of the pantheon of cells that protect us from foreign
invaders, tissue injury and aging
Arch Physiol Biochem. 2013 May 14. [Epub ahead of print]
Obese-derived ASCs show impaired migration and angiogenesis properties.
Pérez LM, Bernal A, San Martín N, Gálvez BG.
Source
Centro Nacional de Investigaciones Cardiovasculares (CNIC) , Madrid , Spain.
Abstract
Abstract Efficient delivery of stem cells to target tissues is a major problem in regenerative medicine.
Adipose derived stem cells have been proposed as important tools in cell therapy for recovering tissues after
damage. Nevertheless, the ability of these ASCs to migrate or invade in order to reach the tissue of interest
has not been tested so far. In this study we present evidence that the ASCs derived from obese subjects
present a detrimental ability to migrate and invade in comparison with ASCs derived from control subjects.
Besides, obese-derived ASCs are unable to respond to certain stimuli and to form enough capillaries after
stimulation. We propose that the use of specific cytokines could overcome these deficiencies of the obese
environment, offering a tool to optimize cell therapy.