The Need for Tissue Engineering

Therapeutic applications of tissue engineering include any disease in which tissue is lost or damaged. For example, in type I diabetes the pancreatic islets of Langerhans are selectively attacked and destroyed by the body's own immune system. Recently, Shapiro and co-workers6 have shown that islet transplantation can, over a short period of time, correct this disease and free its sufferers from reliance on insulin injections and regular glucose checks. A method for generating this structurally...

Foetal Cells in the Maternal Circulation

Over the past 20 years there has been much interest in the development of non-invasive techniques. Of these, isolation of foetal cells from the maternal circulation early in pregnancy could replace existing methods since it should allow exact genetic diagnosis without risks to the foetus. Despite the variety of foetal cells recognised in the maternal circulation, including trophoblast cells, nucleated erythrocytes, leucocytes, platelets and progenitors, non-invasive prenatal diagnosis has been...

Embryonic Stem Cell Opportunities in Developmental Toxicity and Cognitive Disorders

Developmental toxicity comprehends alterations in mammalian development and postnatal physiology that result from chemical exposure during pregnancy. For regulatory and scientific purposes, developmental toxicity is classified in four categories (2) Dysmorphogenesis or structural abnormalities, (3) Intra-uterine growth restriction, and Functional toxicities relate to alterations that are detected after birth, and may be persistent throughout an individual's lifetime. Postnatal development...

Adult Haematopoietic Stem Cells for Liver Regeneration Animal studies

Petersen et al.4 first showed hepatic transdifferentiation in rats, which underwent cross-sex bone marrow transplantation after the hepatic injury was induced by CCl4. Examination of the liver revealed that hepatic cells were from donor origin, as detected by FISH and showed the presence of Y-chromosome in female animals. The other demonstration of hepato-cyte regeneration from bone marrow cells is the extensive repopulation of damaged livers of FAH mice, an inducible animal model of...

References

Bianchi D, Perini M, Baldini S, Panichi N, Giunta S, Rinaldi R. Molecular detection and prevalence investigation of HGV infection among older patients undergoing chronic hemodialysis. J Am Geriatr Soc 1999 47 1040-1041. 2. Hyett JA, Gardener G, Stojilkovic-Mikic T, Finning KM, Martin PG, Rodeck CH, et al. Reduction in diagnostic and therapeutic interventions by non-invasive determination of fetal sex in early pregnancy. Prenat Diagn 2005 25 1111-1116. 3. Stranc LC, Evans JA, Hamerton JL....

Transcriptional Regulation

Batteries of transcription factors have been proposed to control stem cell self-renewal and lineage progression (Fig. 1) by eliciting cascades of gene expression.10 Orphan nuclear receptor TLX is an essential transcriptional regulator of neural stem cell maintenance and self-renewal in the adult brain.11 TLX maintains adult neural stem cells in an undifferentiated, proliferative state. The TLX-expressing cells isolated from adult TLX-heterozygote brains can proliferate, self-renew and...

Foetal Cell Microchimerism

Foetal cell microchimerism, originally described in mice, is defined as the presence of a small number of foetal cells in the maternal blood and tissues without any apparent graft versus host reaction or graft rejection.49 Foetal cells can persist in the maternal blood or tissues for decades, creating a state of physiologic microchimerism in the parous woman. Foetal cells enter the maternal circulation during all pregnancies50 but are very rare. The number of foetal cells entering into the...

The Integrin Family of Adhesion Molecules

Integrins are cell surface receptors that mediate adhesion to cells, to extracellular matrix (ECM) and binding to the components of plasma. Each integrin consists of an a-subunit and a ft-subunit. So far, 18 a-subunits and 8 ft-subunits, which give rise to 24 aft pairs, have been identified in mammals.15 Integrin-mediated adhesion has been implicated in a variety of biological processes, including embryogenesis, angiogenesis, thrombosis, wound healing and cancer spreading. Integrins have...

The cells

The cells represent the living active component of cell-based therapies. Besides the patient-related factors discussed above, any cellular product will be affected also by the preparation technology. ACI offers the advantage of using cells that are stably committed to the appropriate phenotype and can form in vivo stable cartilage tissue, resistant to vascular invasion, mineralisation and ossification23 and therefore the maintenance of this property is essential. However, chondrocyte expansion...

Islet Replacement Therapy

F cell replacement can restore glycaemic control and provide prolonged independence from exogenous insulin.5 Over recent years, advances have been made in islet transplantation methods based upon the initial success of the Edmonton Protocol, developed to treat patients with T1D. In the initial Edmonton Protocol in 2000,100 insulin-independence was observed in 7 patients each of whom received islets isolated from 2 immunologically compatible donor pancreata in conjunction with a...

Adult Haematopoietic Stem Cells for Hepatocyte Generation

Stem cells are undifferentiated and highly clonogenic, with self-renewal capacity and multilineage differentiation potential, and are responsive to environmental cues.9 These properties make them ideal candidates for stem cell-based therapies and tissue engineering. The most studied adult stem cells are haematopoietic stem cells (HSCs), which sustain the formation of blood and immune system throughout life. The bone marrow compartment is largely made up of committed progenitor cells and...

Small RNA Regulators

While transcription factors are essential players in stem cell self-renewal and differentiation,11'24,38,72 post-transcriptional gene regulation is emerging as another essential regulator of development. Many different classes of small non-coding RNAs are present in the brain, with diverse roles including RNA modification and chromatin remodeling.73 Small double-stranded modulatory RNAs have been proposed to regulate the generation of neurons from adult neural stem cells by binding to REST.74...

Streaming Pancreas Islet Cell Kinetics Zajicek G Et Al

Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004 27 1047-1053. 2. Cruz ML, Shaibi GQ, Weigensberg MJ, Spruijt-Metz D, Ball GD, Goran MI. Pediatric obesity and insulin resistance chronic disease risk and implications for treatment and prevention beyond body weight modification. Annu Rev Nutr 2005 25 435-468. 3. Barnett AH, O'Gara G. Diabetes and the Heart (Churchill Livingstone, UK, 2003). 4....

Transplantation of hESCDerived OPCs into SCI

To assess the viability of hESCs as a cell replacement therapy for demyelination and restoration of function, we transplanted hESC-derived OPCs into a rodent model of SCI. We transplanted these cells into rat spinal cords 7 days (acute) and 10 months (chronic) after contusion injury. OPCs transplanted 7 days following SCI survived, migrated 11 mm rostral and 3 mm caudal to the injury site and double labeled for BrdU and CC116 suggesting that the transplanted OPC differentiated into mature...

Challenges for hESCs as a Clinical Cellular Replacement Strategy

The ability to derive myelinogenic transplant populations from stem cells and their success in mediating remyelination in experimental models does not guarantee their success in human demyelinating diseases. The complex nature of the lesioned human CNS presents several challenges that must be well understood and overcome before cellular transplant therapy will be successful. Firstly, transplanted cells may be exposed to the same innate environmental conditions that led to the progression of the...

Bone Marrow and Liver and Gut Cancer

The possibility that BMCs could be involved in carcinogenesis has been explored regarding the liver, female mice were transplanted with male BMCs from (-galactosidase transgenic mice and HCCs were induced by DEN however, none of the tumours was male or X-gal positive.80 However, more extensive studies would be needed to rule out such a possibility, and indeed such an association has been claimed for Helicobacter felis-related murine gastric cancer, where ablation of the indigenous stem cell...

Defining Progenitors Based on Their Expression of Aldehyde Dehydrogenase

Umbilical Cord Blood Transplantation (UCBT) Bone marrow transplantation (BMT) provides a profound and rich history for newly emerging cellular therapies. Over the past 30 years one of the most significant advances in BMT has been the use of allogeneic umbilical cord blood (UCB) as an alternative hematopoietic graft.1-3 Historically, UCB was considered as a discarded by-product from childbirth but now it is routinely banked for transplantation.4'5 UCB offers multiple practical advantages, which...

The Generation of Pancreatic Beta Cells from Stem Cells Intra and Extrapancreatic Sources

Guppy, Tariq G. Fellous and Malcolm R. Alison Diabetes mellitus is an incurable metabolic disease characterised by hyperglycaemia, which results largely from either the autoimmune destruction of the pancreatic beta cells (Type I diabetes, T1D), or from insufficient production of insulin to meet the increased resistance of peripheral tissues to the action of insulin (Type II diabetes, T2D), both of which may have severe clinical consequences. Currently, allogeneic islet...

Where Do the Cancers Arise

The assessment of DNA alterations in tumour cells allows a precise determination of their clonality. Where HBV is involved, there is no doubt that the integration of HBV-DNA into the hepatic genome is a significant event in hepatocarcinogenesis.1,35,36 Moreover inspection of viral integration sites amongst tumour cells clearly indicates that each tumour is monoclonal, i.e. derived from a single cell.37-40 Likewise, studies of HCC clonality based on restriction fragment length polymorphisms of...

Lymphocyte Homing and the Structural Organisation of the Immune System

In an organised immune system cell migration needs to be directed. Tissue and microenvironment-selective lymphocyte homing is the basis for this organisation. The regulated expression of adhesion molecules and their ligands and of chemokines and their receptors underlie the structural and systemic organisations of the immune system, being essential for leukocyte development, lymphocyte recirculation, immune surveillance, and effector lymphocyte differentiation and targeting. In other words,...

The Immunoregulatory Role of Mesenchymal Stem Cells

Francesco Dazzi and Jennifer Timoshanko Recently, several provocative links have been made between stem cells and the induction of specific tolerance. Embryonic, hematopoietic and mes-enchymal stem cells (MSC) all display immunoregulatory properties, and have successfully induced tolerance in a variety of rodent and large animal studies. MSCs have been reported to evade the immune system and suppress immune responses to nominal and transplantation antigens. Evidence for these conclusions has...

Stem Cells of the Liver and

If we believe that tumours have their origins in normal stem cells, or at least in cells with sufficient longevity to acquire multiple genetic mutations, then we need to appreciate normal cell turnover in the liver and intestine. Foetal liver is a source of bipotential progenitor cells (hepatoblasts) as seen by their extensive colonisation of the diseased livers of rats after transplantation.8 In postnatal animals, hepatocytes are highly differentiated cells with multiple synthetic and...

Contributors

Centre for Diabetes and Metabolic Medicine Queen Mary's School of Medicine and Dentistry Institute of Cell and Molecular Science 4 Newark Street, Whitechapel London E1 2AT, UK Centre for Diabetes and Metabolic Medicine Queen Mary's School of Medicine and Dentistry Institute of Cell and Molecular Science 4 Newark Street, Whitechapel London E1 2AT, UK Stem Cell Safety Sciences Laboratory Department of Animal Sciences University of Wisconsin-Madison 1675 Observatory Drive Madison, WI53706, USA...

Epigenetic Control

The transition of stem cells from self-renewal to differentiated state is accompanied by global changes in gene expression. Genes active in proliferative stem progenitor cells are silenced, whereas cell type-specific genes are turned on. This progression is the result of selective expression of transcription factors in concert with chromatin remodeling and epigenetic modifications, including covalent histone modification and DNA methylation of CpG dinucleotides. Transcription in eukaryotic...