Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

Andreazzoli, Massimiliano; Angeloni, Debora; Broccoli, Vania; Demontis, Gian Carlo

doi:10.3389/fspas.2017.00002

Cited by 14 publications

(12 citation statements)

References 71 publications

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“…Second, we used a 3D-clinostat to simulate microgravity, whereas other studies used different types of equipment, including rotating wall vessels and parabolic flight campaign (PFC) equipment 17 , 18 , 23 – 26 , 30 , which could affect the results. Previous microgravity results have also been contradictory, and these reports have been extensively reviewed already 31 , 32 . Data from astronauts on space shuttles 30 differ from the results that are obtained in some simulated microgravity environments.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential

Hagiwara

Higashibata

Ogawa

et al. 2018

Sci Rep

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Endothelial progenitor cell (EPC) transplantation is beneficial for ischemic diseases such as critical limb ischemia and ischemic heart disease. The scarcity of functional EPCs in adults is a limiting factor for EPC transplantation therapy. The quality and quantity culture (QQc) system is an effective ex vivo method for enhancing the number and angiogenic potential of EPCs. Further, microgravity environments have been shown to enhance the functional potential of stem cells. We therefore hypothesized that cells cultured with QQc under microgravity may have enhanced functionality. We cultured human peripheral blood mononuclear cells using QQc under normal (E), microgravity (MG), or microgravity followed by normal (ME) conditions and found that ME resulted in the most significant increase in CD34+ and double positive Dil-Ac-LDL-FITC-Ulex-Lectin cells, both EPC markers. Furthermore, angiogenic potential was determined by an EPC-colony forming assay. While numbers of primitive EPC-colony forming units (pEPC-CFU) did not change, numbers of definitive EPC-CFU colonies increased most under ME conditions. Gene-expression profiling also identified increases in angiogenic factors, including vascular endothelial growth factor, under MG and ME conditions. Thus, QQc along with ME conditions could be an efficient system for significantly enhancing the number and angiogenic potential of EPCs.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential

Hagiwara

Higashibata

Ogawa

et al. 2018

Sci Rep

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“…Using different methods to MGS, four labs showed MGS caused morbidity or slowed embryonic development for 4 days after fertilization and before uterine implantation [18][19][20][21]. These alternate MGS modalities are reviewed elsewhere [22,23]. The major mechanism for slowed growth and morbidity caused by MGS was apparently the activation of the mitogen-activated protein kinase (MAPK8/9) subfamily known as stress-activated protein kinase (SAPK, also known as jun kinases [JNKs]) [19] which is reviewed below.…”

Section: Mgs Creates Morbidity or Slows Growth Of The Postfertilization Preimplantation Mouse Embryomentioning

confidence: 99%

Effects of Gravity, Microgravity or Microgravity Simulation on Early Mammalian Development

Ruden

Bolnick

Awonuga

et al. 2018

Stem Cells and Development

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Plant and animal life forms evolved mechanisms for sensing and responding to gravity on Earth where homeostatic needs require responses. The lack of gravity, such as in the International Space Station (ISS), causes acute, intra-generational changes in the quality of life. These include maintaining calcium levels in bone, maintaining muscle tone, and disturbances in the vestibular apparatus in the ears. These problems decrease work efficiency and quality of life of humans not only during microgravity exposures but also after return to higher gravity on Earth or destinations such as Mars or the Moon. It has been hypothesized that lack of gravity during mammalian development may cause prenatal, postnatal and transgenerational effects that conflict with the environment, especially if the developing organism and its progeny are returned, or introduced de novo, into the varied gravity environments mentioned above. Although chicken and frog pregastrulation development, and plant root development, have profound effects due to orientation of cues by gravity-sensing mechanisms and responses, mammalian development is not typically characterized as gravity-sensing. Although no effects of microgravity simulation (MGS) on mouse fertilization were observed in two reports, negative effects of MGS on early mammalian development after fertilization and before gastrulation are presented in four reports that vary with the modality of MGS. This review will analyze the positive and negative mammalian early developmental outcomes, and enzymatic and epigenetic mechanisms known to mediate developmental responses to simulated microgravity on Earth and microgravity during spaceflight experiments. We will update experimental techniques that have already been developed or need to be developed for zero gravity molecular, cellular, and developmental biology experiments.

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“…Interestingly, activation of lymphocytes prior to exposure to analog microgravity partially or completely abrogated the inhibitory effect of microgravity on lymphocyte motility. Our data suggest that the loss of locomotory function and T cell activation is probably due to lesion(s) in transmembrane signaling possibly involving calcium independent PKC isoforms such as delta and epsilon [6,14,18,19]. Gene expression data from our laboratory on normal and activated peripheral blood lymphocytes cultured in modeled microgravity indicate that selective genes involved in inflammatory processes are affected by changes in gravity.…”

Section: Lymphocyte Locomotionmentioning

confidence: 73%

“…In a study done by Thiel et al [25] they suggest that long-term in vitro studies should be taken into consideration to have supporting detailed and prolonged data analysis in hopes to identify and understand adaptation mechanisms of the immune system in altered gravity. Additionally, Andreazzoli et al [19], proposes that extensive knowledge of cellular and molecular mechanisms of gravity and its influence on T cells is an invaluable requirement for the provision of therapeutic or preventive targets to keep the bone and immune systems of astronauts fully functional during long-term space missions as well as regular people with immune deficiencies.…”

Section: Resultsmentioning

confidence: 99%

Lymphocyte Signaling and Function in Altered Physiological Environments

Mann¹,

Okoro²,

Sodipe³

et al. 2019

Lymphocytes

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The immune system is the body's defense against infectious organisms and other invaders. It is our immune system that keeps us healthy as we drift through a sea of pathogens. Healthy immune function depends on meticulous regulation of lymphocyte activation. Previous studies have shown unfavorable effects of μg on several physiological systems, including a significant reduction of the adaptive immune response. Lymphocyte movement through interstitium is critically important for the immune response. Thus, the activation of lymphocytes depends on various factors such as cell-to-cell contact due to temporary contact, permanent aggregation or by the uptake of soluble factors such as interleukin 1. Microgravity induced loss of lymphocyte locomotory activity, along with diminished lymphocyte activation, can be counteracted by nutritional supplements such as nucleotides. A study conducted by Andreazzoli et al., proposes that the knowledge of cellular and molecular mechanisms of gravity and its influence on T cells is required for creating the provision of therapeutic and possible preventive targets to keep the bone and immune systems of astronauts fully functional during long-term space missions, in addition to aiding regular people with immune deficiencies. When an immune system is compromised it can lead to various infections as well as cancerous growths. Discovering the ins and outs of the lymphocyte regulatory pathways can account for controlling and studying medicinal treatments for all forms or immune disorders. Therefore, studying both the long-term and short-term effects of microgravity is of great significance, as it has an invalidation nature that affects how the regulators of the immune system are readily able to function.

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Microgravity, Stem Cells, and Embryonic Development: Challenges and Opportunities for 3D Tissue Generation

Cited by 14 publications

References 71 publications

Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential

Effectiveness of endothelial progenitor cell culture under microgravity for improved angiogenic potential

Effects of Gravity, Microgravity or Microgravity Simulation on Early Mammalian Development

Lymphocyte Signaling and Function in Altered Physiological Environments

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