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PubMed2007

Microfabrication of fractal polymeric structures for capillary morphogenesis: applications in therapeutic angiogenesis and in the engineering of vascularized tissue.

Microfabrication techniques were combined with fractal algorithms to realize polymeric scaffolds resembling capillary networks. The scaffolds were seeded with human endothelial cells in monoculture as well as in coculture with human fibroblasts. To enhance the process of angiogenesis, endothelial cells were transfected with an adenoviral vector carrying the gene for human tissue kallikrien. The results demonstrate that both the presence of a structured scaffold as well as fibroblasts in coculture contribute synergically to the promotion of a metabolically active network. The fractal scaffolds have several possible applications for example in vascularized tissue engineering and therapeutic angiogenesis. A broader implication of these results is that cell-extra cellular matrix and cell-cell interactions cooperate dynamically both at a biochemical as well as microstructural level.

Algorithms↗

PubMed2026

ChromID: A Protocol for Mapping Protein Chromatin Interactions in Living Cells.

Chromatin modifications regulate genome function by recruiting proteins that control transcription, genome organization, and DNA repair. Identifying the proteins associated with specific chromatin modifications is therefore essential for understanding how these regulatory processes operate. Traditional approaches, including chromatin immunoprecipitation and affinity purification coupled to mass spectrometry, have uncovered many chromatin-associated proteins. However, they often rely on crosslinking and chromatin fragmentation, which can disrupt native chromatin architecture and limit the detection of transient interactions. Here, we describe a proximity-labeling protocol for identifying the chromatin-dependent protein interactome associated with specific chromatin marks, termed ChromID. ChromID uses engineered chromatin readers (eCRs) fused to a promiscuous biotin ligase, which labels proteins in the immediate vicinity of the targeted chromatin mark. The protocol includes in vivo biotin labeling, nuclear extract preparation, streptavidin-based enrichment, and tryptic digestion for downstream LC-MS/MS analysis. The protocol has been validated across multiple cell types and chromatin contexts and can be extended to other chromatin-associated proteins, providing a versatile approach to profile chromatin-associated proteomes within their native cellular environment. Key features • Maps proteins associated with different chromatin modifications in living cells using engineered chromatin readers fused to TurboID, BASU, or other promiscuous biotin ligases. • Preserves native chromatin organization and captures transient chromatin-associated interactions that are often lost during conventional affinity purification workflows. • Validated across multiple chromatin contexts, including histone modifications, DNA methylation, transcription factors, RNA polymerase II, and DNA damage-associated chromatin states. • Applicable to diverse cell types and organisms and adaptable to other chromatin-associated proteins, including transcription factors and chromatin regulators.

Biotin proximity labeling↗

PubMedDate not supplied

[Meniscus replacement: current aspects in the field of tissue engineering].

Tissue engineering offers new opportunities for meniscus repair and replacement. In this field different approaches are being studied to genererate a meniscus subsitute by a combination of a matrix scaffold, cells and specific stimuli. MENISCUS REPLACEMENT BY ACELLUAR MATRICES: For meniscus replacement the matrix material has to meet high biomechanical demands. Besides implant geometry, the material properties and a secure intraarticular attachment are important preconditions for implant function. A collagen scaffold has already been applied clinically for partial meniscus replacement. Scaffolds made of synthetic, bioabsorbable polymers and small intestine submucosa have been employed in animal studies. Following implantation, matrices are invaded by cells and undergo a process of remodeling. Formation of fibrocartilage repair tissue has been observerd. The biomechanical quality of implants and their effect on cartilage preservation have to be studied further. CELLULAR SEEDING OF MATRICES FOR MENSICUS REPLACEMENT: Advanced biological and biomechanical implant quality might be achieved by seeding matrices with cells in vitro. However, the ideal type of cell for this purpose has not yet been identified. Autologous mensicus cells, articular chondrocytes and mesenchymal stem cells represent possible cellular sources. Additional stimuli, such as cytokines and mechanical forces, and techniques of genetic engineering might further contribute to enhance the quality of engineered tissue.

Biocompatible Materials↗

PubMed2004

Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiation.

The nuclear transcription factor Nurr1 is involved in the development and maintenance of the midbrain dopaminergic (DA) neuronal phenotype. We analysed the cellular and biological effects of Nurr1 during embryonic stem (ES) cell differentiation using the ROSA26-engineered Tet-inducible ES cell line J1-rtTA that does not express transgenes in mature neurons. Induction of Nurr1 at nestin-positive precursor and later stages of ES cell differentiation produced a non-neuronal DA cell type including functional DA transporters. In these cells, we found a clear correlation between Nurr1 and TH gene expression and specific midbrain DA cellular markers such as AADC, AHD2 and calbindin. Nurr1 did not alter gene expression of non-DA neuronal phenotypes and did not influence other midbrain developmental transcription factors, such as Otx1, Otx2, En-1, GBX2, Pitx3 and lmx1b. In addition, Nurr1 expression was required for maintenance of the DA phenotype and mediated up-regulation of the tyrosine kinase Ret and associated trophic factor GDNF-family receptors alpha 1, 2, and 4. This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain-like DA biochemical and functional cellular phenotype independent of neurogenesis.

Animals↗

PubMed1999

Engineering of the myosin-ibeta nucleotide-binding pocket to create selective sensitivity to N(6)-modified ADP analogs.

Distinguishing the cellular functions carried out by enzymes of highly similar structure would be simplified by the availability of isozyme-selective inhibitors. To determine roles played by individual members of the large myosin superfamily, we designed a mutation in myosin's nucleotide-binding pocket that permits binding of adenine nucleotides modified with bulky N(6) substituents. Introduction of this mutation, Y61G in rat myosin-Ibeta, did not alter the enzyme's affinity for ATP or actin and actually increased its ATPase activity and actin-translocation rate. We also synthesized several N(6)-modified ADP analogs that should bind to and inhibit mutant, but not wild-type, myosin molecules. Several of these N(6)-modified ADP analogs were more than 40-fold more potent at inhibiting ATP hydrolysis by Y61G than wild-type myosin-Ibeta; in doing so, these analogs locked Y61G myosin-Ibeta tightly to actin. N(6)-(2-methylbutyl) ADP abolished actin filament motility mediated by Y61G, but not wild-type, myosin-Ibeta. Furthermore, a small fraction of inhibited Y61G molecules was sufficient to block filament motility mediated by mixtures of wild-type and Y61G myosin-Ibeta. Introduction of Y61G myosin-Ibeta molecules into a cell should permit selective inhibition by N(6)-modified ADP analogs of cellular processes dependent on myosin-Ibeta.

Actins↗

PubMed1984

Applications of recombinant DNA technology to the pulp and paper industry.

New gene selection techniques (Recombinant DNA) are currently available to exploit useful properties of various biological systems hitherto regarded as interesting but of little or no immediate commercial value. The application of genetic engineering techniques to problems in the Pulp and Paper Industry are many. As a first step these techniques are being used to provide much needed fundamental information on the cellular and molecular mechanisms involved in the expression of extra-cellular enzymes that degrade lignocellulosic pulping wastes. The information gleaned from the studies on cellulolytic fungi and bacteria can be used to genetically engineer a yeast or bacterium capable of converting pulping wastes into ethanol and other useful by-products.

Journal Article↗

PubMed2004

Telomerized presenescent osteoblasts prevent bone mass loss in vivo.

Previously, we showed that human osteoblasts expressing the human telomerase reverse transcriptase (hTERT) gene exhibited specific survival advantages--the result of breaching the replicative senescence barrier and maintaining the phenotypic and functional properties of primary osteoblasts in vitro over the total replicative capacity of primary osteoblasts. We postulated that rejuvenated osteoblasts may have a potential to correct bone loss or osteopenia in age-related osteoporotic diseases. In the present study, we studied whether telomerized presenescent osteoblasts prevent bone mass loss in vivo. After obtaining the informed consent from a patient with osteoarthritis who underwent the arthroplastic knee surgery, osteoblastic cells were isolated from donor bone sample. We transfected the gene encoding hTERT into human osteoblastic cells. Human bone fragments from a donor were incubated with human hTERT-transfected presenescent (in vitro aged) osteoblasts or mock-transfected presenescent osteoblasts in culture medium containing Matrigel. We subcutaneously implanted human bone fragments with telomerized presenescent osteoblasts or primary presenescent osteoblasts as three-dimensional Matrigel xenografts in severe combined immunodeficiency (SCID) mice (each group: six mice) and analyzed the grafts at 6 weeks after implantation. We also determined whether telomerized osteoblasts affect the bone-forming capacity in vivo, using a well-established mouse transplantation model in which ceramic hydroxyapatite/tricalcium phosphate particles are used as carrier vehicle. Telomerized presenescent osteoblasts were rejuvenated, and maintained the functional properties of young osteoblasts in vitro. Bone mineral content (BMC) and bone mineral density (BMD) were measured by ash weight and dual-energy X-ray absorptiometry, respectively. Whereas BMC and BMD of human bone fragments, which were inoculated with aged osteoblasts in SCID mice, decreased with time, telomerized presenescent osteoblasts maintained the BMC and BMD of human bone fragments, indicating that telomerized and rejuvenated osteoblasts may be functional to prevent bone mass loss in vivo. In xenogenic transplants, telomerized osteoblasts generated more bone tissue with lamellar bone structure and cellular components, than did control osteoblasts. These findings suggest that telomerized/rejuvenated presenescent osteoblasts may be used in the development of tissue engineering or cell-based therapy for bone regeneration and repair.

Animals↗

PubMedDate not supplied

The effect of hydrodynamic shear on 3D engineered chondrocyte systems subject to direct perfusion.

Bioreactors allowing direct-perfusion of culture medium through tissue-engineered constructs may overcome diffusion limitations associated with static culturing, and may provide flow-mediated mechanical stimuli. The hydrodynamic stress imposed on cells within scaffolds is directly dependent on scaffold microstructure and on bioreactor configuration. Aim of this study is to investigate optimal shear stress ranges and to quantitatively predict the levels of hydrodynamic shear imposed to cells during the experiments. Bovine articular chondrocytes were seeded on polyestherurethane foams and cultured for 2 weeks in a direct perfusion bioreactor designed to impose 4 different values of shear level at a single flow rate (0.5 ml/min). Computational fluid dynamics (CFD) simulations were carried out on reconstructions of the scaffold obtained from micro-computed tomography images. Biochemistry analyses for DNA and sGAG were performed, along with electron microscopy. The hydrodynamic shear induced on cells within constructs, as estimated by CFD simulations, ranged from 4.6 to 56 mPa. This 12-fold increase in the level of applied shear stress determined a 1.7-fold increase in the mean content in DNA and a 2.9-fold increase in the mean content in sGAG. In contrast, the mean sGAG/DNA ratio showed a tendency to decrease for increasing shear levels. Our results suggest that the optimal condition to favour sGAG synthesis in engineered constructs, at least at the beginning of culture, is direct perfusion at the lowest level of hydrodynamic shear. In conclusion, the presented results represent a first attempt to quantitatively correlate the imposed hydrodynamic shear level and the invoked biosynthetic response in 3D engineered chondrocyte systems.

Animals↗

PubMed2005

Isolation of primary endothelial and stromal cell cultures of the corpus cavernosum penis for basic research and tissue engineering.

OBJECTIVES: Primary cell cultures derived from the corpus cavernosum are frequently used as in vitro models to define cellular mechanisms involved in erectile function. However, previous studies often lack detailed isolation protocols or a precise characterisation of the culture composition excluding especially contaminating fibroblasts. This study aimed at critically analysing and reproducing reported isolation methods, as well as establishing new procedures to receive highly pure and morphologically differentiated endothelial, smooth muscle and fibroblastic cells derived from the human penis. METHODS: We evaluated numerous isolation and enrichment techniques using cavernosal tissue from 57 patients. Assessment factors displayed the purity, cell yield, practicability and reproducibility. The purity in cultured cells was analysed using immunocytochemistry and Western blots. RESULTS: An enzymatic protocol was established for the isolation and cultivation of cavernosal endothelial cells with an impressive purity of 98.0+/-0.8%. In contrast, already published nearly pure smooth muscle cell cultures were not reproducible in our laboratory. Meaningful evidence for an overwhelming presence of fibroblasts in these widely accepted pure smooth muscle cell cultures is presented. CONCLUSION: Endothelial cell cultures derived from human corpora cavernosa are reproducible and reliable to serve for cell culture-based investigations of the endothelial dysfunction. The discrepancy in the purity of smooth muscle cell cultures might reflect laboratory and tissue source factors, lacking an exclusion of fibroblasts in other studies or changes in stromal phenotype under culture conditions. Further research is necessary to clarify a possible plasticity between smooth muscle cells and (myo)fibroblasts and assess functional properties.

Adult↗

PubMed2000

Low-copy plasmids can perform as well as or better than high-copy plasmids for metabolic engineering of bacteria.

Multicopy plasmids are often chosen for the expression of recombinant genes in Escherichia coli. The high copy number is generally desired for maximum gene expression; however, the metabolic burden effects that usually result from multiple plasmid copies could prove to be detrimental for maximum productivity in certain metabolic engineering applications. In this study, low-copy mini-F plasmids were compared to high-copy pMB1-based plasmids for production of two metabolites in E. coli: polyphosphate (polyP) and lycopene derived from isopentenyl diphosphate (IPP). The stationary-phase accumulation of polyP on a per cell basis was enhanced approximately 80% when either high- or low-copy plasmids were used, from 120 micromol/g DCW without augmented polyP kinase (PPK) activity to approximately 220 micromol/g DCW. The cell density of the high-copy plasmid-containing culture at stationary phase was approximately 24% lower than the low-copy culture and 30% lower than the control culture. This difference in cell density is likely a metabolic burden effect and resulted in a lower overall product concentration for the high-copy culture (approximately 130 micromol/L culture) relative to the low-copy culture (approximately 160 micromol/L culture). When the gene for DXP (1-deoxy-D-xylulose 5-phosphate) synthase, the first enzyme in the IPP mevalonate-independent biosynthetic pathway, was expressed from the tac promoter on multicopy and low-copy plasmids, lycopene production was enhanced two- to threefold over that found in cells expressing the chromosomal copy only. Cell growth and lycopene production decreased substantially when isopropyl beta-D-thiogalactosidase (IPTG) was added to the high-copy plasmid-containing culture, suggesting that overexpression of DXP synthase was a significant metabolic burden. In the low-copy plasmid-containing culture, no differences in cell growth or lycopene production were observed with any IPTG concentrations. When dxs was placed under the control of the arabinose-inducible promoter (P(BAD)) on the low-copy plasmid, the amount of lycopene produced was proportional to the arabinose concentration and no significant changes in cell growth resulted. These results suggest that low-copy plasmids may be useful in metabolic engineering applications, particularly when one or more of the substrates used in the recombinant pathway are required for normal cellular metabolism.

Acid Anhydride Hydrolases↗

PubMedDate not supplied

Integration of cell culture and microfabrication technology.

Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

Biosensing Techniques↗

PubMed2006

Engineered early embryonic cardiac tissue retains proliferative and contractile properties of developing embryonic myocardium.

Embryonic myocardium has a high rate of cell proliferation and regulates cellular proliferation, contractile function, and myocardial architecture in response to changes in external mechanical loads. However, the small and complex three-dimensional (3D) structure of the embryonic myocardium limits our ability to directly investigate detailed relationships between mechanical load, contractile function, and cardiomyocyte proliferation. We developed a novel 3D engineered early embryonic cardiac tissue (EEECT) from early embryonic ventricular cells to test the hypothesis that EEECT retains the proliferative and contractile properties of embryonic myocardium. We combined freshly isolated White Leghorn chicken embryonic ventricular cells at Hamburger-Hamilton (HH) stage 31 (day 7 of a 46-stage, 21-day incubation period), collagen type I, and matrix factors to construct cylindrical-shaped EEECTs. We studied tissue architecture, cell proliferation patterns, and contractile function. We then generated engineered fetal cardiac tissue (EFCT) from HH stage 40 (day 14) fetal ventricular cells for direct comparison with EEECT. Tissue architecture was similar in EEECT and EFCT. EEECT maintained high cell proliferation patterns by culture day 12, whereas EFCT decreased cell proliferation rate by culture day 9 (P < 0.05). EEECT increased active contractile force from culture day 7 to day 12. The culture day 12 EEECT contractile response to the beta-adrenergic stimulation was less than culture day 9 EFCT (P < 0.05). Cyclic mechanical stretch stimulation induced myocardial hyperplasia in EEECT. Results indicate that EEECT retains the proliferative and contractile properties of developing embryonic myocardium and shows potential as a robust in vitro model of developing embryonic myocardium.

Animals↗

PubMed2003

Engineering of the extracellular matrix: working toward neural stem cell programming and neurorestoration--concept and progress report.

In the concept of neurorestoration, cellular and structural elements that have been lost are replaced, and their function is restored. Central to this therapeutic strategy is the transplantation of neural progenitor cells such as clonogenically expanded stem cells. Stem cells make decisions regarding fate and patterning in response to external environmental signals. The therapeutic effectiveness of neural stem cells may be facilitated by the ability to manipulate these signals in a temporal and spatially appropriate fashion. Artificial deoxyribonucleic acid and artificial protein technology combines elements of protein engineering, molecular biology, and recombinant deoxyribonucleic acid technology to produce proteins with functional domains derived from naturally occurring proteins and represents a potentially powerful tool to modulate stem cell behavior. To this end, we have developed three artificial extracellular matrix proteins that incorporate the active domain of hJagged1 and hDelta1 into an elastin backbone. hJagged1 and hDelta1 are members of the DSL family of ligands to the Notch receptor, a signaling system that is very important in development and is the strongest known signal to instruct neural progenitor cells to choose glial fates over neuronal fates. The successful cloning of the artificial genes was confirmed by test digestions with appropriate restriction enzymes as well as direct deoxyribonucleic acid sequencing. In addition, we have demonstrated that all three artificial extracellular matrix proteins express at a high level in a prokaryotic host. This report describes the concept and progress in an entirely novel and previously unreported approach to modulate neural stem cell behavior. Its future application could include in vitro processing of stem cells before transplantation, supporting and programming the cells after transplantation, as well as the development of bioactive biomaterials.

Cell Physiological Phenomena↗

PubMed1990

Targeting, import, and processing of nuclear gene-encoded proteins into mitochondria and peroxisomes.

I have herein discussed two gene-enzyme families in maize whose protein products participate to purge toxic oxidants from cells, and are thus of importance to all aerobic organisms. We have demonstrated that plant mitochondria import precursor proteins (i.e., preSOD-3) in a manner analogous to other eukaryotic cells. The "transit peptide" (TP) of preSOD-3 is 31 amino acids long and has similar properties to other reported TPs for mitochondrial and chloroplastic proteins. Import to peroxisomes is uniquely different from that for mitochondria and chloroplasts in that no consensus presequence seems to be involved. Instead, targeting signals seem to be integral parts of peroxisomal proteins. These studies are important from a genetic engineering perspective in that it is not only important to express genes in specific tissues, but also within specific subcellular compartments. Expression of donor genes in appropriate cellular compartments of host cells will be critical for maintaining a stable, functional protein in the plant. Manipulation of metabolic pathways in plants requires that engineered proteins be efficiently and effectively expressed in the correct subcellular compartment and during the appropriate developmental time frame. The use of engineered proteins with altered topogenicity may not only prove useful in studying the role(s) of such proteins in metabolism, they may also serve to enhance our understanding of inter-organellar communication within the cell.

Amino Acid Sequence↗

PubMed2001

Construction of an Escherichia coli knockout strain for functional analysis of tRNA(Asp).

The specific aminoacylation of tRNA is critical for translation of the genetic code. A molecular description of aminoacylation requires knowledge of the relevant three-dimensional structures, biochemical parameters and the structure-function relationship of the synthetase and its substrate tRNA. Extensive structural and biochemical data are available on the aspartic acid system of Escherichia coli, but there is a paucity of cellular functional data. We have developed a system to overcome this deficiency by engineering an E. coli knockout tRNA(Asp) strain, thereby allowing a penetrating analysis of tRNA(Asp) structure and function under conditions that prevail in the cell.

Acylation↗

PubMed2004

Lewis Wolpert discusses development and depression. Interview by Joanne Clough.

Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology at University College, London, UK. His research interests focus on the mechanisms that are involved in embryonic development. Lewis originally trained as a civil engineer in South Africa but in 1955 made the move to research in cellular biology at King's College, London. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. Lewis was also made a Fellow of the Royal Society of Literature in 1999 and has presented science on both radio and TV for several years. He was awarded The Royal Society Michael Faraday Prize in 2000 for his contribution to the public understanding of science, most notably through his Chairmanship of the Committee for the Public Understanding of Science (COPUS; 1993-1998). He is the author of numerous books, including Malignant Sadness: The Anatomy of Depression, Principles of Development, The Unnatural Nature of Science and The Triumph of the Embryo. He also writes a regular column for The Independent.

Animals↗

PubMed2002

Keratinocyte stem cells: a commentary.

For many years it has been widely accepted that stem cells play a crucial role in adult tissue maintenance. The concept that the renewing tissues of the body contain a small subcompartment of self-maintaining stem cells, upon which the entire tissue is dependent, is also now accepted as applicable to all renewing tissues. Gene therapy and tissue engineering are driving considerable interest in the clinical application of such hierarchically organized cellular compartments. Recent initial observations have provided a tantalizing insight into the large pluripotency of these cells. Indeed, scientists are now beginning to talk about the possible totipotency of some adult tissue stem cells. Such work is currently phenomenologic, but analysis of data derived from genomics and proteomics, identifying the crucial control signals involved, will soon provide a further impetus to stem cell biology with far reaching applications. The epidermis with its relatively simple structure, ease of accessibility, and the ability to grow its cells in vitro is one obvious target tissue for testing stem cell manipulation theories. It is crucial, however, that the normal keratinocyte stem cell is thoroughly characterized prior to attempting to manipulate its pluripotency. This commentary assesses the data generated to date and critically discusses the conclusions that have been drawn. Our current level of understanding, or lack of understanding, of the keratinocyte stem cell is reviewed.

Biomarkers↗

PubMed2005

Bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (MSCs) contribute to the regeneration of mesenchymal tissues, and are essential in providing support for the growth and differentiation of primitive hemopoietic cells within the bone marrow microenvironment. Techniques are now available to isolate human MSCs and manipulate their expansion in vitro under defined culture conditions without change of phenotype or loss of function. Mesenchymal stem cells have generated a great deal of interest in many clinical settings, including that of regenerative medicine, immune modulation and tissue engineering. Studies have already demonstrated the feasibility of transplanted MSCs providing crucial new cellular therapy. In this review, many aspects of the MSC will be discussed, with the main focus being on clinical studies that describe the potential of MSCs to treat patients with hematological malignancies who are undergoing chemotherapy and/or radiotherapy.

Bone Marrow Cells↗