In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

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Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

The improper distribution of chromosomes during mitosis compromises cellular functions and can reduce cellular fitness or contribute to malignant transformation. As a countermeasure, higher eukaryotes have developed strategies for eliminating mitosis-incompetent cells, one of which is mitotic catastrophe. Mitotic catastrophe is driven by a complex and poorly understood signalling cascade but, from a functional perspective, it can be defined as an oncosuppressive mechanism that precedes (and is distinct from) apoptosis, necrosis or senescence. Accordingly, the disruption of mitotic catastrophe precipitates tumorigenesis and cancer progression, and its induction constitutes a therapeutic endpoint.

Mitotic catastrophe: a mechanism for avoiding genomic instability

Mitotic catastrophe (MC) has long been considered as a mode of cell death that results from premature or inappropriate entry of cells into mitosis and can be caused by chemical or physical stresses. Whereas it initially was depicted as the main form of cell death induced by ionizing radiation, it is today known to be triggered also by treatment with agents influencing the stability of microtubule, various anticancer drugs and mitotic failure caused by defective cell cycle checkpoints. Although various descriptions explaining MC exist, there is still no general accepted definition of this phenomenon. Here, we present evidences indicating that death-associated MC is not a separate mode of cell death, rather a process ('prestage') preceding cell death, which can occur through necrosis or apoptosis. The final outcome of MC depends on the molecular profile of the cell.

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Death through a tragedy: mitotic catastrophe

Background:The indications for fat grafting are increasing steadily. In microfat grafting, thin injection cannulas are used. The authors describe their experience of fat injection with even thinner injection needles up to 27 gauge. The fat used for this purpose is processed into “nanofat.” Clinical

Nanofat Grafting: Basic Research and Clinical Applications

Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating numerous genetic and degenerative disorders. Among them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson's and Alzheimer's diseases, arthritis, and muscular, skin, lung, eye, and digestive disorders as well as aggressive and recurrent cancers could be successfully treated by stem cell-based therapies. This review focuses on the recent advancements in adult stem cell biology in normal and pathological conditions. We describe how these results have improved our understanding on critical and unique functions of these rare sub-populations of multipotent and undifferentiated cells with an unlimited self-renewal capacity and high plasticity. Finally, we discuss some major advances to translate the experimental models on ex vivo and in vivo expanded and/or differentiated stem cells into clinical applications for the development of novel cellular therapies aimed at repairing genetically altered or damaged tissues/organs in humans. A particular emphasis is made on the therapeutic potential of different tissue-resident adult stem cell types and their in vivo modulation for treating and curing specific pathological disorders.

Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies.

Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues

Chronic exposure of many human hepatoma cell lines to a low dose (LD) of doxorubicin induced a senescence-like phenotype (SLP) accompanied by enlargement of cells and increased senescence-associated beta-galactosidase activity LD doxorubicin-induced SLP was preceded by multinucleation and downregulation of multiple proteins with mitotic checkpoint function, including CENP-A, Mad2, BubR1, and Chk1 LD doxorubicin-treated cells eventually underwent cell death through mitotic catastrophe When we investigated whether LD doxorubicin-induced cell death shares biochemical characteristics with high dose (HD) doxorubicin-induced apoptosis in Huh-7 cells, we observed that externalization of phosphatidyl serine and release of mitochondrial cytochrome c into the cytosol was associated with both types of cell death However, propidium iodide exclusion assays showed that membrane integrity was lost in the initial phase of LD doxorubicin-induced cell death through mitotic catastrophe, whereas it was lost during the late phase of HD doxorubicin-induced apoptosis Furthermore, HD doxorubicin-induced apoptosis but not LD doxorubicin-induced mitotic catastrophe led to transient activation of NF-kappaB and strong, sustained activations of p38, c-Jun N-terminal kinase, and caspases Collectively, these results indicate that different doses of doxorubicin activate different regulatory mechanisms to induce either apoptosis or cell death through mitotic catastrophe

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype.

Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood.

Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis

Young-Woo Eom

Papers

Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues

Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype.

Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood.

Cdc2 and Cdk2 play critical roles in low dose doxorubicin-induced cell death through mitotic catastrophe but not in high dose doxorubicin-induced apoptosis

Bcl-xL blocks high dose doxorubicin-induced apoptosis but not low dose doxorubicin-induced cell death through mitotic catastrophe.