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Amino acid compositions and uses thereof

A composition, technology of amino acids, for use in reproductive, migration, maturation and/or cell differentiation, pulmonary and skin disorders,] described herein for the treatment of GI in the field of weakened mechanical and immune barriers

Active Publication Date: 2019-07-26
UNIV OF FLORIDA RES FOUNDATION INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

TPN also weakens mechanical and immune barriers

Method used

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  • Amino acid compositions and uses thereof
  • Amino acid compositions and uses thereof
  • Amino acid compositions and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0227] Example 1 - AA-ORS Increases Crypt Count and Villus Length in Intestinal Tissue from Irradiated Mice

[0228] Intestinal tissue from irradiated mice (5-15 Gy) treated with AA-ORS showed a significant increase in crypt counts (N) per circumference. Since crypts are formed by regenerative units, these results indicate an increase in the number of epithelial progenitor cells. Similarly, villi length was significantly increased at all radiation doses treated with AA-ORS compared with saline treatment ( Figure 1B ). This is consistent with increased progenitor cell proliferation and / or longer epithelial cell survival prior to natural shedding.

[0229] Crypt survival curves were modeled using a single-hit multi-target cell survival model to assess biological effects. Without limiting constant cell sensitivity, N values ​​were 10.4 ± 0.2 and 5.3 ± 0.1 (P < 0.001), indicating almost doubling of progenitor units per circumference compared to controls. When limiting a const...

Embodiment 2-A

[0233] Example 2-AA-ORS Promotes Migration of Intestinal Epithelial Cells

[0234] Ileum sections of irradiated mice treated with AA-ORS showed increased crypt counts. As the villous epithelium continues to renew, the cells also migrate continuously along the crypt-villus axis. 23 Epithelial cells undergo further maturation and differentiation as the cells move along the villi, and then migrate to the tips of the villi where they are shed by the phenomenon of anoikis. 24 Study of cell proliferation using EdU incorporation.

[0235] Cells were found to migrate from the base of the crypt to the tip of the villi within about 72 hours. Ileum sections from non-irradiated mice showed that cells (incorporating EdU) reached the tip of the villi at various times (75 ± 0.9 hours; n = 10 mice), with an average of 76.5 hours. AA-ORS treatment for 6 days did not result in a significant difference in the length covered by migrating cells between 0 and 5 Gy irradiated mice (153.5±6 mm vs....

Embodiment 3-A

[0236] Example 3 - AA-ORS Increases Sodium and Chlorine Absorption

[0237] AA-ORS increased villus height and proliferation in the crypt cell region. To determine whether increased villus height leads to functionally mature and differentiated villous epithelial cells, isotope flux studies were performed to measure sodium and chloride uptake.

[0238] Unirradiated mice have 1.9±0.6ueq.cm 2 .h- 1 The net sodium absorption (JNetNa) and 1.9±0.4ueq.cm 2 .h- 1 The net chlorine absorption (JNetC1) ( Figure 3A to Figure 3B ). JNetNa (1.9±0.6μeq.cm 2 .h- 1 Relative to 0.1±0.0μeq.cm 2 .h- 1 ; P2 .h- 1 Relative to -0.9±0.4μeq.cm 2 .h- 1 )reduce. AA-ORS treatment resulted in 0Gy (3.9±0.7ueq.cm 2 .h- 1 ; p2 .h- 1 ; p Figure 3A ). Similarly, AA-ORS treatment resulted in 0Gy (4.1±0.6ueq.cm 2 .h- 1 ; p2 .h- 1 ; p Figure 3B ).

[0239] These studies suggest that AA-ORS-induced increases in villous height are functional by showing increased electrolyte uptake capacity and...

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Abstract

The invention provides compositions and methods for promoting stem cell and / or progenitor cell proliferation and / or differentiation. The provided compositions may be useful in treating a disease or condition that is related to mucosal barrier function, e.g., wound healing, treating skin conditions (e.g., atopic dermatitis, psoriasis, bed sores, or condition related to the aging of skin), treatinga lung disorders (e.g., asthma), a condition related to improving mucosal barrier function, and / or treating injury to GI mucosa in a subject in need thereof. The invention also provides methods for promoting the proliferation and / or differentiation of stem cells and / or the progenitor cells in a subject in need of such treatment by administering a composition. The ability to stimulate the proliferation and / or differentiation of stem cells and / or the progenitor cells in vivo, ex vivo and / or in vitro provides tremendous benefit. The compositions can be used to increase stem cell populations in vivo, ex vivo and / or in vitro. Stem cell transplantation provides treatments and / or cures of many disease states, degeneration and / or injury.

Description

[0001] related application [0002] This application claims priority under 35 U.S.C. § 119(e) of U.S. Provisional Application U.S.S.N. 62 / 403,965, filed October 4, 2016, and U.S.S.N. Each is incorporated herein by reference. Background technique [0003] Human intestinal epithelial cells arise from a fixed stem cell population functionally located in the lower part of the intestinal crypts, which in mice includes rapidly cycling crypt-basal columnar cells (CBC) and more quiescent Paneth cells above the crypts. "+4" cells. 14-16 These stem cells give rise to absorptive enterocytes, mucous cells, Paneth cells and enteroendocrine cells. 17 Differentiation of each cell type occurs as cells migrate up the villi (absorptive, mucous, and endocrine cells) or concentrate downward at the bottom of the crypts (Paneth cells). The multiple mechanisms involved in these complex events are not fully understood. [0004] Radiation and / or chemotherapy can cause severe damage to the lining o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/195A61K31/197A61K31/198
CPCA61K31/198A61P1/00A61P1/04A61P1/16A61P1/18A61P11/00A61P11/06A61P17/00A61P17/02A61P17/04A61P17/06A61P25/00A61P27/02A61P27/16A61P31/04A61P31/10A61P31/12A61P35/00A61P3/10A61P37/04A61P37/06A61P37/08A61P43/00A61P5/00A61P7/00A61P9/00A61P9/10Y02A50/30A61K2300/00A61K31/405
Inventor S·维德亚瑟格R·古普塔L·尹A·格罗舍P·G·奥库尼夫S·加托D·丹尼森
Owner UNIV OF FLORIDA RES FOUNDATION INC
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