scholarly journals Can laboratory model systems instruct human limb regeneration?

Development ◽  
2019 ◽  
Vol 146 (20) ◽  
pp. dev181016 ◽  
Author(s):  
Ben D. Cox ◽  
Maximina H. Yun ◽  
Kenneth D. Poss
2015 ◽  
Vol 112 (44) ◽  
pp. E5904-E5904 ◽  
Author(s):  
Ruth A. Hufbauer ◽  
Marianna Szűcs ◽  
Emily Kasyon ◽  
Courtney Youngberg ◽  
Michael J. Koontz ◽  
...  

1997 ◽  
Vol 352 (1359) ◽  
pp. 1377-1384 ◽  
Author(s):  
R. K. Grencis

Despite many years of study, relatively little is known about the effector mechanisms that operate against intestine–dwelling nematodes. Most of the current understanding comes from studies of laboratory model systems in rodents. It is clear that when an intestinal helminth infection takes place the immune system generates a strong Th2–mediated response, which regulates a variety of responses characteristic of helminth infections such as eosinophilia, intestinal mastocytosis and elevated IgE production. The ability to modulate the host's immune response in vivo with cytokine–specific monoclonal antibodies and recombinant cytokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with which to dissect the potential effector mechanisms operating. In the absence of a T–cell compartment the host is unable to expel the parasite. If a Th1–dominated response is generated, protective immunity is almost universally compromised. Thus, it would appear that some aspect of Th2–mediated response controls effector mechanisms. Although it is clear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non–specific inflammatory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not through the high–affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector leucocytes and antibody. There is little evidence to support a protective role for eosinophilia in any system. New data also imply that , although interleukin 4 (IL–4) is generally important (and can exert effects independent of an adaptive immune response), it is not always sufficient to mediate protection; other Th2 cytokines (e.g. IL–13) may warrant closer investigation. It is apparent that a number of potential Th2–controlled effector mechanisms (some of which may be particularly important at mucosal surfaces) remain to be explored. Overall, it is likely that worm expulsion is the result of a combination of multiple mechanisms, some of which are more critical to some species of parasite than to others.


2021 ◽  
Vol 12 ◽  
Author(s):  
Can Aztekin

Therapeutic implementation of human limb regeneration is a daring aim. Studying species that can regrow their lost appendages provides clues on how such a feat can be achieved in mammals. One of the unique features of regeneration-competent species lies in their ability to seal the amputation plane with a scar-free wound epithelium. Subsequently, this wound epithelium advances and becomes a specialized wound epidermis (WE) which is hypothesized to be the essential component of regenerative success. Recently, the WE and specialized WE terminologies have been used interchangeably. However, these tissues were historically separated, and contemporary limb regeneration studies have provided critical new information which allows us to distinguish them. Here, I will summarize tissue-level observations and recently identified cell types of WE and their specialized forms in different regeneration models.


2019 ◽  
Author(s):  
V.V. Babenko ◽  
A.K. Golomidova ◽  
P.A. Ivanov ◽  
M.A. Letarova ◽  
E.E. Kulikov ◽  
...  

AbstractTailed bacteriophages (Caudovirales order) are omnipresent on our planet. Their impressive ecological and evolutionary success largely relies on the bacteriophage potential to adapt to great variety of the environmental conditions found in the Biosphere. It is believed that the adaptation of bacteriophages, including short time scale adaptation, is achieved almost exclusively via the (micro)evolution processes. In order to analyze the major mechanisms driving adaptation of phage genomes in a natural habitat we used comparative genomics of G7C-like coliphage isolates obtained during 7 years period from the feces of the horses belonging to a local population. The data suggest that even at this relatively short time scale the impact of various recombination events overwhelms the impact of the accumulation of point mutations. The access to the large pool of the genes of a complex microbial and viral community of the animal gut had major effect on the evolutionary trajectories of these phages. Thus the “real world” bacteriophage evolution mechanisms may differ significantly from those observed in the simplified laboratory model systems.


2019 ◽  
Author(s):  
Tian Qin ◽  
Chun-mei Fan ◽  
Ting-zhang Wang ◽  
Long Yang ◽  
Wei-liang Shen ◽  
...  

ABSTRACTWhile the capacity to regenerate tissues or limbs is limited in mammals including humans, unlike us, axolotls are able to regrow entire limbs and major organs. The wound blastema have been extensively studied in limb regeneration. However, due to the inadequate characterization and coordination of cell subpopulations involved in the regeneration process, it hinders the discovery of the key clue for human limb regeneration. In this study, we applied unbiased large-scale single-cell RNA sequencing to classify cells throughout the adult axolotl limb regeneration process. We computationally identified 7 clusters in regenerating limbs, including the novel regeneration-specific mitochondria-related cluster supporting regeneration through energy providing and the COL2+ cluster contributing to regeneration through cell-cell interactions signals. We also discovered the dedifferentiation and re-differentiation of the COL1+/COL2+ cellular subpopulation and uncovered a COL2-mitochondria sub-cluster supporting the musculoskeletal system regeneration. On the basis of these findings, we reconstructed the dynamic single-cell transcriptome atlas of adult axolotl limb regenerative process, and identified the novel regenerative mitochondria-related musculoskeletal populations, which yielded deeper insights into the crucial interactions between cell clusters within the regenerative microenvironment.


1999 ◽  
Vol 13 (6) ◽  
pp. 509-516 ◽  
Author(s):  
Derek M McKay

The idea that the enteric microflora play a role in the pathogenesis or pathophysiology of inflammatory bowel disease (IBD) is not new. Indeed, identification of an infective cause for chronic IBD, and particularly for Crohn’s disease, has been the focus of extensive research efforts. During the 1990s, there has been a noticeable re-emergence of interest in the link between bacteria and functional bowel disorders, and the value of antibiotic therapy to treat gut inflammatory disorders. A variety of experimental evidence from both laboratory model systems and clinical investigations is reviewed with respect to a pivotal role for enteric bacteria in gut inflammation. The voluminous scientific literature on this subject precludes any comprehensive synopsis of the area; instead, pertinent studies are cited to illustrate the ability of bacteria and their products to evoke or exacerbate gut inflammation.


1991 ◽  
Vol 54 (6) ◽  
pp. 436-442 ◽  
Author(s):  
LONE GRAM

The purpose of the present study has been to develop simple fish preservation techniques applicable at artisanal level in developing countries in the tropical zone. Mesophilic motile Aeromonas spp. which were classified as specific spoilage bacteria of Nile perch (Lates niloticus) from Lake Victoria stored at ambient temperature were inhibited in laboratory model systems using NaCl, potassium sorbate, and liquid smoke. Growth was not detected when the salt concentration exceeded 5% or the temperature was below 5°C. At 25–37°C growth occurred within 24 h when no preservation was applied, but a combination of 5% salt and 1000 ppm sorbate inhibited growth at 25–37°C. Liquid smoke inhibited growth at 37°C only when an initial low inoculum (102 CFU/ml) was used. Based on the model experiments, trials were carried out in Kenya and a lightly preserved fish product stable at ambient temperature was developed. The addition of 1.5% salt (w/w) and 1500 ppm sorbate (w/w) followed by 3 d of sun-drying resulted in a lightly brown, well preserved fish product which could be produced at artisanal level and was palatable to local consumers. Good agreement was seen between results from model experiments and trials with fish.


2018 ◽  
Vol 13 (1) ◽  
pp. 184-198
Author(s):  
Anna A. Vetrova ◽  
Vladimir A. Zabelin ◽  
Anastasia A. Ivanova ◽  
Lyubov A. Adamenko ◽  
Yanina A. Delegan ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Kevin Roarty ◽  
Gloria V. Echeverria

While numerous therapies are highly efficacious in early-stage breast cancers and in particular subsets of breast cancers, therapeutic resistance and metastasis unfortunately arise in many patients. In many cases, tumors that are resistant to standard of care therapies, as well as tumors that have metastasized, are treatable but incurable with existing clinical strategies. Both therapy resistance and metastasis are multi-step processes during which tumor cells must overcome diverse environmental and selective hurdles. Mechanisms by which tumor cells achieve this are numerous and include acquisition of invasive and migratory capabilities, cell-intrinsic genetic and/or epigenetic adaptations, clonal selection, immune evasion, interactions with stromal cells, entering a state of dormancy or senescence, and maintaining self-renewal capacity. To overcome therapy resistance and metastasis in breast cancer, the ability to effectively model each of these mechanisms in the laboratory is essential. Herein we review historic and the current state-of-the-art laboratory model systems and experimental approaches used to investigate breast cancer metastasis and resistance to standard of care therapeutics. While each model system has inherent limitations, they have provided invaluable insights, many of which have translated into regimens undergoing clinical evaluation. We will discuss the limitations and advantages of a variety of model systems that have been used to investigate breast cancer metastasis and therapy resistance and outline potential strategies to improve experimental modeling to further our knowledge of these processes, which will be crucial for the continued development of effective breast cancer treatments.


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