Current Stem Cell Research & Therapy

ISSN: 1574-888X

Current Stem Cell Research & Therapy
Volume 2, Number 2, May 2007

Contents


Recruitment of Endogenous Neural Progenitor Cells by Malignant Neoplasms of the Central Nervous System Pp. 113- 119
Henry Klassen
[Abstract]


Cell Based Approaches for Myocardial Regeneration and Artificial Myocardium Pp. 121-127
Jorge Genovese, Miguel Cortes-Morichetti, Emmanuel Chachques, Giacomo Frati, Amit Patel and Juan C. Chachques
[Abstract]


Nanotopographical Control of Human Osteoprogenitor Differentiation Pp. 129-138
Matthew J. Dalby, Nikolaj Gadegaard, Adam S.G. Curtis and Richard O.C. Oreffo
[Abstract]


Generation and Transplantation of Dopaminergic Neurons Derived from Embryonic Stem Cells Pp. 139-147
Aparna Khanna, Anna Maria Swistowska, Mahendra S. Rao and Xianmin Zeng
[Abstract]


Reduced-Intensity Stem Cell Transplantation for Hematological Malignancies: Current Status and the Future Pp. 149-162
Koji Kato, Yasser Khaled and Shin Mineishi
[Abstract]


Reduced-Intensity Transplantation in the Treatment of Haematological Malignancies: Current Status and Future Prospects Pp. 163-188
Suparno Chakrabarti and Hubertus C.E. Buyck
[Abstract]




Abstracts

[Back to top]
Recruitment of Endogenous Neural Progenitor Cells by Malignant Neoplasms of the Central Nervous System
Henry Klassen

It is proposed here that malignancies of the central nervous system (CNS) are capable of recruiting non-malignant CNS precursor cells and that doing so worsens the course of the disease. In particular, the argument is put forward that such tumors can activate resident neural stem cells, attract them or their progeny to the tumor site, and induce them to proliferate. What begins as a normal wound repair response by the recruited cells can eventually result in augmentation of the tumor. In support of this hypothesis, evidence consistent with the ideas proposed is presented. Since these recruited cells are non-malignant, it should be possible to interfere with this process. This would not necessarily remove the threat posed by the cancer, but could beneficially impact patients by slowing progression. Interfering with recruitment could simultaneously serve to block autocrine stimulation by tumor cells. In contrast, introducing exogenous stem cells could exacerbate the recruitment process unless measures are taken to preclude this possibility. Finally, it is worth noting that the situation described in the current hypothesis might apply to a variety of other stem and precursor cell-containing systems throughout the body.


[Back to top]
Cell Based Approaches for Myocardial Regeneration and Artificial Myocardium
Jorge Genovese, Miguel Cortes-Morichetti, Emmanuel Chachques, Giacomo Frati, Amit Patel and Juan C. Chachques

Ischemic myocardial disease, the main cause of heart failure, is a major public health and economic problem. Given the aging population, heart failure is becoming an increasing clinical issue and a substantial financial burden. Thus, research in heart failure is of relevant interest and importance, involving specialties such as cellular and molecular biology, tissue engineering, genetics, biophysics and electrophysiology. Stem cell-based regenerative therapy is undergoing experimental and clinical trials in order to limit the consequences of decreased contractile function and compliance of damaged ventricles following myocardial infarction or in patients presenting non-ischemic dilated cardiomyopathies. This biological approach is particularly attractive due to the potential for myocardial regeneration with a variety of myogenic and angiogenic cell types. The development of a bio-artificial myocardium using biological or synthetic matrix is a new challenge.


[Back to top]
Nanotopographical Control of Human Osteoprogenitor Differentiation
Matthew J. Dalby, Nikolaj Gadegaard, Adam S.G. Curtis and Richard O.C. Oreffo

Current load-bearing orthopaedic implants are produced in ‘bio-inert’ materials such as titanium alloys. When inserted into the reamed bone during hip or knee replacement surgery the implants interact with mesenchymal populations including the bone marrow. Bio-inert materials are shielded from the body by differentiation of the cells along the fibroblastic lineage producing scar tissue and inferior healing. This is exacerbated by implant micromotion, which can lead to capsule formation.

Thus, next-generation implant materials will have to elicit influence over osteoprogenitor differentiation and mesenchymal populations in order to recruit osteoblastic cells and produce direct bone apposition onto the implant.

A powerful method of delivering cues to cells is via topography. Micro-scale topography has been shown to affect cell adhesion, migration, cytoskeleton, proliferation and differentiation of a large range of cell types (thus far all cell types tested have been shown to be responsive to topographical cues). More recent research with nanotopography has also shown a broad range of cell response, with fibroblastic cells sensing down to 10 nm in height.
Initial studies with human mesenchymal populations and osteoprogenitor populations have again shown strong cell responses to nanofeatures with increased levels of osteocalcin and osteopontin production from the cells on certain topographies. This is indicative of increased osteoblastic activity on the nanotextured materials. Looking at preliminary data, it is tempting to speculate that progenitor cells are, in fact, more responsive to topography than more mature cell types and that they are actively seeking cues from their environment.

This review will investigate the range of nanotopographies available to researchers and our present understanding of mechanisms of progenitor cell response. Finally, it will make some speculations of the future of nanomaterials and progenitor cells in tissue engineering.


[Back to top]
Generation and Transplantation of Dopaminergic Neurons Derived from Embryonic Stem Cells
Aparna Khanna, Anna Maria Swistowska, Mahendra S. Rao and Xianmin Zeng

Human embryonic stem cells (hESCs) can be propagated as undifferentiated cells over multiple passages and thus offer a renewable source of a wide range of cell types for use in research and cell-based therapies. Because of the important roles of dopaminergic (DA) neurons in modulating motor control, and in particular that the selective degeneration of DA neurons in midbrain cause the neurodegenerative disorder Parkinson’s disease (PD), there has been significant interest in using hESC-derived DA neurons as a source of cells for drug screening, discovery and transplant purposes. Different strategies have evolved to generate appropriately mature DA neurons that have been purified and/or enriched by one of several selection techniques. In this manuscript we discuss recent results, review the remarkable progress that has been made in the field, and compare these results with those obtained from mouse ESCs (mESCs).


[Back to top]
Reduced-Intensity Stem Cell Transplantation for Hematological Malignancies: Current Status and the Future
Koji Kato, Yasser Khaled and Shin Mineishi

Reduced-intensity stem cell transplantation (RIST) has opened a new era for hematopoietic stem cell transplantation (HSCT). It was developed based on the knowledge that graft-versus-tumor (GVT) effect is the main anti-tumor effect in allogeneic HSCT. Because RIST is associated with less morbidity and mortality, it can be applied to many patients who could not undergo conventional HSCT. Experiences in the last decade clarified many issues related to RIST. For example, graft-versus-host disease (GVHD) in RIST may differ in character compared to conventional HSCT. Also, it is now known that intensity of conditioning is important in disease control, and the optimal regimens may be different for each disease or for each disease status. There are still many unsolved questions, and large prospective randomized trials are necessary to resolve these.


[Back to top]
Reduced-Intensity Transplantation in the Treatment of Haematological Malignancies: Current Status and Future Prospects
Suparno Chakrabarti and Hubertus C.E. Buyck

The concept of reduced intensity conditioning (RIC) in allogeneic transplantation had challenged our conventional wisdom about the necessity of high-dose chemo-radiotherapy in order to achieve donor engraftment. The feasibility of RIC in elderly and infirm patients who would not otherwise be considered suitable for a conventional allogeneic transplantation caused a surge of interest in RIC procedures in the late 90s and early part of this decade which was however, not tempered by the balanced need for clinical trials. Although the initial expectations of reduction in graft-versus-host-disease (GVHD) were belied by the high incidences of GVHD, the importance of GVHD, particularly chronic, in controlling haematological malignancies with poor prognosis was often well exemplified. In addition, the conventional outcome measures in allogeneic transplantation such as 100- day mortality became irrelevant in the era of RIC due to reduction in early regimen-related toxicities. This did not always translate to improved overall survival due to late attritions from relapse, GVHD or late infectious complications. The enthusiasm for performing RIC in malignant diseases seems to have reached a plateau, but its true potential probably remains unexplored. In light of our current understanding of RIC, this article will highlight the future of this procedure in haematological malignancies.