Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications.

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regeneration . Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators.

Stem and Progenitor Cells in Human Cardiopulmonary Development and Regeneration.

Already during embryonic development, the heart and the lung are thoroughly connected organs. Their interdependence allows our survival in the terrestrial environment by coupling cardiac output and gas exchange. The knowledge on developmental processes involving stem and progenitor cells is crucial to understand the onset of human cardiopulmonary diseases.

Stem Cell Banking and Its Impact on Cardiac Regenerative Medicine.

Cardiovascular diseases, including heart failure, are the most frequent cause of death annually, even higher than any other pathologies. Specifically, patients who suffer from myocardial infarction may encounter adverse remodeling processes of the heart that can ultimately lead to heart failure. Prognosis of patients affected by heart failure is very poor with 5-year mortality close to 50 %.

Tracking chromatid segregation to identify human cardiac stem cells that regenerate extensively the infarcted myocardium.

Rationale: According to the immortal DNA strand hypothesis, dividing stem cells selectively segregate chromosomes carrying the old template DNA, opposing accumulation of mutations resulting from nonrepaired replication errors and attenuating telomere shortening.

Objective: Based on the premise of the immortal DNA strand hypothesis, we propose that stem cells retaining the old DNA would represent the most powerful cells for myocardial regeneration.

Methods And Results: Division of human cardiac stem cells (hCSCs) by nonrandom and random segregation of chromatids was documented by clonal assay of bromodeoxyuridine-tagged hCSCs.

Evidence for human lung stem cells.

Background: Although progenitor cells have been described in distinct anatomical regions of the lung, description of resident stem cells has remained elusive.

Methods: Surgical lung-tissue specimens were studied in situ to identify and characterize human lung stem cells. We defined their phenotype and functional properties in vitro and in vivo.

Adult human adipose tissue contains several types of multipotent cells.

Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells.

Myocyte turnover in the aging human heart.

Rationale: The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology.

Objective: The effects of age and gender on the magnitude of myocyte regeneration and the origin of newly formed cardiomyocytes were determined.

Methods And Results: The interaction of myocyte replacement, cellular senescence, growth inhibition, and apoptosis was measured in normal female (n=32) and male (n=42) human hearts collected from patients 19 to 104 years of age who died from causes other than cardiovascular diseases.

Stem cell update: highlights from the 2010 Lugano Stem Cell Meeting.

The 2010 edition of the Lugano Stem Cell Meeting, under the auspices of the Swiss center of excellence in cardiovascular diseases "Cardiocentro Ticino" and the Swiss Stem Cell Foundation, offered an update on clinical, translational, and biotechnological advances in regenerative science and medicine pertinent to cardiovascular applications. Highlights from the international forum ranged from innate mechanisms of heart repair, safety, and efficacy of ongoing and completed clinical trials, novel generations of stem cell biologics, bioengineered platforms, and regulatory processes. In the emerging era of regenerative medicine, accelerating the critical path from discovery to product development will require integrated multidisciplinary teams to ensure timely translation of new knowledge into validated algorithms for practice adoption.

Stem cell biobanks.

Stem cells contribute to innate healing and harbor a promising role for regenerative medicine. Stem cell banking through long-term storage of different stem cell platforms represents a fundamental source to preserve original features of stem cells for patient-specific clinical applications. Stem cell research and clinical translation constitute fundamental and indivisible modules catalyzed through biobanking activity, generating a return of investment.

Progenitor cells from the explanted heart generate immunocompatible myocardium within the transplanted donor heart.

Rationale: Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans.

Objective: Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy that implements the use of cardiac progenitor cells from the recipient to repopulate the donor heart with immunocompatible cardiomyocytes and coronary vessels.

Methods And Results: A large number of cardiomyocytes and coronary vessels were created in a rather short period of time from the delivery, engraftment, and differentiation of cardiac progenitor cells from the recipient.

Identification of a coronary vascular progenitor cell in the human heart.

Primitive cells capable of generating small resistance arterioles and capillary structures in the injured myocardium have been identified repeatedly. However, these cells do not form large conductive coronary arteries that would have important implications in the management of the ischemic heart. In the current study, we determined whether the human heart possesses a class of progenitor cells that regulates the growth of endothelial cells (ECs) and smooth muscle cells (SMCs) and vasculogenesis.

Inhibition of ref-1 stimulates the production of reactive oxygen species and induces differentiation in adult cardiac stem cells.

Redox effector protein-1 (Ref-1) plays an essential role in DNA repair and redox regulation of several transcription factors. In the present study, we examined the role of Ref-1 in maintaining the redox status and survivability of adult cardiac stem cells challenged with a subtoxic level of H2O2 under inhibition of Ref-1 by RNA interference. Treatment of cardiac stem cells with a low concentration of H2O2 induced Ref-1-mediated survival signaling through phosphorylation of Akt.

"In vitro" and multicolor phenotypic characterization of cell subpopulations identified in fresh human adipose tissue stromal vascular fraction and in the derived mesenchymal stem cells.

Background: The stromal vascular fraction (SVF) is a heterogeneous cell population derived from the adipose tissue. There is still a lack of information concerning the characterization of the cell subpopulations constituting the SVF as well as its mesenchymal and haematopoietic potential. Furthermore there are great variations in its phenotypical characterization.

Tumor and metastasis suppression by the human RNASET2 gene.

The region 6q27 from human chromosome 6 has been reported to contain one or more tumor suppressor genes on the basis of cytogenetic, molecular and functional studies. We have recently carried out a detailed analysis of a candidate gene from 6q27 to evaluate its putative role as a tumor suppressor gene involved in ovarian cancer pathogenesis. The RNASET2 gene was shown to behave as a class II tumor suppressor and abolish the tumorigenic potential of an ovarian cancer-derived cell line.