Large-scale automated hollow fiber bioreactor expansion of human umbilical cord-derived mesenchymal stromal cells for neurological disorders. Neurodegenerative diseases make up a large group of neurological diseases and remain one of the greatest challenges and burdens for humanity. Diseases such as amyotrophic lateral sclerosis, Alzheimer’s disease, stroke or spinal cord injury are often associated with astrogliosis (astrogliosis) with symptoms of inflammation.
- The regenerative, paracrine and immunomodulatory properties of human mesenchymal stromal cells (hMSCs) can affect the above components, thus opening up new therapeutic possibilities for regenerative medicine.
- Of particular interest are hMSCs derived from umbilical cord (UC) tissue due to their origin, properties and lack of ethical paradigms. The aim of this study was to establish standard protocols for good manufacturing practice ( GMP ) for the operational and large-scale isolation, characterization, expansion and comparison of the properties of UC-hMSC cells collected in T vials compared to use of a large-scale bioreactor system. .
- Human UC-hMSC, isolated by culture technique from Wharton’s Jelly explant, was collected at 75% confluence and cultured in tissue culture bottles. UC-hMSCs obtained before / after cryopreservation and after collection in the bioreactor were fully characterized in terms of immunomodulatory “mesenchymicity”, oncogenicity and genetic stability, aging and cell doubling properties and gene expression traits . Our study demonstrates an efficient and simple technique for increasing UC-hMSC.
- Collecting UC-hMSCs using classical and large-scale methods did not alter UC-hMSC aging, genetic stability or carcinogenicity in vitro. We observed comparable growth and immunomodulatory capacity of fresh, frozen and expanded UC-hMSC.
- We found no differences in the ability to differentiate towards adipogenic, osteogenic, and chondrogenic lineages between classical and large-scale UC-hMSC expansion methods. Both methods made it possible to derive genetically stable cells with typical mesenchymal characteristics.
- Interestingly, we found that UC-hMSC grown in a bioreactor showed significantly increased levels of neural growth factor (NGF) mRNA expression and reduced levels of insulin growth factor (IGF), while IL4 , IL6, IL8,
- TGFb and VEGF expression levels remained at a similar level. Cultivation of UC-hMSC using a large-scale automated closed bioreactor expansion system under GMP conditions does not alter basic “mesenchymal” characteristics and cell quality.
- Our study was designed to pave the way for the translation of known basic research data on human UC-MSC into future clinical trials in patients with neurological and immunocompromised disorders.
- Industrial production of UC-hMSC will then be approved by regulatory authorities under the criteria for advanced therapy medicinal products (ATMP) prior to clinical use and approval for use in patients.

The relaxation factor of endothelial origin produced and released by the arteries and veins is nitric oxide.
- The aim of this study was to determine whether nitric oxide (NO) is responsible for vascular smooth muscle relaxation induced by endothelial-derived relaxation factor (EDRF). EDRF is an unstable humoral substance released by arteries and veins that mediates the action of dependent endothelial vasodilators.
- NO is an unstable, endothelium-independent vasodilator that is released by vasodilators such as nitroprusside and glyceryl trinitrate. We have repeatedly observed that the effect of NO on vascular smooth muscle is very similar to that of EDRF. In the present study, the vascular effect of EDRF released from a pulmonary artery and a perfused vein of cattle was compared with that of NO delivered by overflow through endothelial strips of cascading arteries and veins.
- EDRF was indistinguishable from NO as both were unstable (t1 / 2 = 3-5 s), inactivated by pyrogallol or superoxide anion, stabilized by superoxide dismutase, and inhibited by oxyhemoglobin or potassium. Both EDRF and NO produced a comparable increase in the cyclic accumulation of GMP in the artery and vein, and this cyclic accumulation of GMP was inhibited by pyrogallol, oxyhemoglobin, potassium and methylene blue.
- EDRF was chemically identified as NO or a labile nitrous species by two procedures. First, like NO, EDRF released from newly isolated aortic endothelial cells reacted with hemoglobin to form nitrosylemoglobin.
- Second, EDRF and NO similarly promoted the diazotization of sulphanilic acid and produced the same reaction product after coupling with N- (1-naphthyl) ethylenediamine. Therefore, EDRF released from an artery and a vein has biological and chemical properties identical to NO.
The cyclic GMP -AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
Providing epidemiological, virological and immunological parameters in HIV + patients defined as long-term progression (LTnP) may be the key to understanding the natural history of HIV disease and its therapeutic approach.
- The aim of this study was to identify factors that delay the onset of HIV-related symptoms in HIV-infected patients with low progression. We interviewed several people defined as LTnP according to the following criteria.
- Patients were asymptomatic with documented HIV infection for at least 8 years, had never been treated with antiretroviral therapy and had CD4 levels always above 500 / cmm. They were tested every 6 months for the following tests: virus isolation, viral strain characterization; Quantitative DNA-PCR; HIV p24 antigen in serum, plasma viraemia, neutralizing antibodies to autologous and heterologous primary isolates.
Human Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Hu-96T | DL Develop | 96T | 470.4 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Mu-48T | DL Develop | 48T | 522 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Mu-96T | DL Develop | 96T | 673.2 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-p-48T | DL Develop | 48T | 591.6 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-p-96T | DL Develop | 96T | 769.2 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Ra-48T | DL Develop | 48T | 372 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Ra-96T | DL Develop | 96T | 466.8 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Rb-48T | DL Develop | 48T | 544.8 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Rb-96T | DL Develop | 96T | 704.4 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Sh-48T | DL Develop | 48T | 626.4 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Sh-96T | DL Develop | 96T | 817.2 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Si-48T | DL Develop | 48T | 626.4 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Si-96T | DL Develop | 96T | 817.2 EUR |
Bovine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-b-48Tests | Reddot Biotech | 48 Tests | 592.8 EUR |
Bovine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-b-96Tests | Reddot Biotech | 96 Tests | 820.8 EUR |
Canine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-c-48Tests | Reddot Biotech | 48 Tests | 566.4 EUR |
Canine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-c-96Tests | Reddot Biotech | 96 Tests | 783.6 EUR |
Chicken Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Ch-48Tests | Reddot Biotech | 48 Tests | 540 EUR |
Chicken Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Ch-96Tests | Reddot Biotech | 96 Tests | 746.4 EUR |
Equine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Eq-48Tests | Reddot Biotech | 48 Tests | 606 EUR |
Equine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Eq-96Tests | Reddot Biotech | 96 Tests | 840 EUR |
Human Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Hu-48Tests | Reddot Biotech | 48 Tests | 348 EUR |
Human Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Hu-96Tests | Reddot Biotech | 96 Tests | 470.4 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Mu-48Tests | Reddot Biotech | 48 Tests | 514.8 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Mu-96Tests | Reddot Biotech | 96 Tests | 709.2 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-p-48Tests | Reddot Biotech | 48 Tests | 592.8 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-p-96Tests | Reddot Biotech | 96 Tests | 820.8 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Ra-48Tests | Reddot Biotech | 48 Tests | 345.6 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Ra-96Tests | Reddot Biotech | 96 Tests | 468 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Rb-48Tests | Reddot Biotech | 48 Tests | 540 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Rb-96Tests | Reddot Biotech | 96 Tests | 746.4 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Sh-48Tests | Reddot Biotech | 48 Tests | 632.4 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Sh-96Tests | Reddot Biotech | 96 Tests | 877.2 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Si-48Tests | Reddot Biotech | 48 Tests | 632.4 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Si-96Tests | Reddot Biotech | 96 Tests | 877.2 EUR |
Bovine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-b-48Tests | Reddot Biotech | 48 Tests | 619.2 EUR |
Bovine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-b-96Tests | Reddot Biotech | 96 Tests | 859.2 EUR |
Canine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-c-48Tests | Reddot Biotech | 48 Tests | 591.6 EUR |
Canine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-c-96Tests | Reddot Biotech | 96 Tests | 819.6 EUR |
Chicken Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Ch-48Tests | Reddot Biotech | 48 Tests | 564 EUR |
Chicken Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Ch-96Tests | Reddot Biotech | 96 Tests | 781.2 EUR |
Equine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Eq-48Tests | Reddot Biotech | 48 Tests | 633.6 EUR |
Equine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Eq-96Tests | Reddot Biotech | 96 Tests | 879.6 EUR |
Human Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Hu-48Tests | Reddot Biotech | 48 Tests | 362.4 EUR |
Human Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Hu-96Tests | Reddot Biotech | 96 Tests | 490.8 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Mu-48Tests | Reddot Biotech | 48 Tests | 536.4 EUR |
Mouse Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Mu-96Tests | Reddot Biotech | 96 Tests | 741.6 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-p-48Tests | Reddot Biotech | 48 Tests | 619.2 EUR |
Porcine Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-p-96Tests | Reddot Biotech | 96 Tests | 859.2 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Ra-48Tests | Reddot Biotech | 48 Tests | 360 EUR |
Rat Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Ra-96Tests | Reddot Biotech | 96 Tests | 488.4 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Rb-48Tests | Reddot Biotech | 48 Tests | 564 EUR |
Rabbit Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Rb-96Tests | Reddot Biotech | 96 Tests | 781.2 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Sh-48Tests | Reddot Biotech | 48 Tests | 661.2 EUR |
Sheep Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Sh-96Tests | Reddot Biotech | 96 Tests | 918 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Si-48Tests | Reddot Biotech | 48 Tests | 661.2 EUR |
Monkey Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Si-96Tests | Reddot Biotech | 96 Tests | 918 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Gu-48T | DL Develop | 48T | 568.8 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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DLR-IL4-Gu-96T | DL Develop | 96T | 736.8 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Gu-48Tests | Reddot Biotech | 48 Tests | 566.4 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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RD-IL4-Gu-96Tests | Reddot Biotech | 96 Tests | 783.6 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Gu-48Tests | Reddot Biotech | 48 Tests | 591.6 EUR |
Guinea pig Interleukin 4 (IL4) ELISA Kit |
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RDR-IL4-Gu-96Tests | Reddot Biotech | 96 Tests | 819.6 EUR |
GMP-140/ Rat GMP- 140 Elisa Kit |
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ELA-E0602r | Lifescience Market | 96 Tests | 1063.2 EUR |
Cyclic GMP Antibody |
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abx022640-02ml | Abbexa | 0.2 ml | 1128 EUR |
Cyclic di-GMP |
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B7839-.5 | ApexBio | 500 µg | 217.2 EUR |
Cyclic di-GMP |
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B7839-1 | ApexBio | 1 mg | 362.4 EUR |
Cyclic-di-GMP |
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HY-107780 | MedChemExpress | 10mM/1mL | 4454.4 EUR |
EGF GMP, CF |
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PR15112CF | Neuromics | 200 ug | 481.2 EUR |
SCF GMP, CF |
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PR15113CF | Neuromics | 50 ug | 1687.2 EUR |
BDNF GMP, CF |
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PR15134CF | Neuromics | 5 ug | 763.2 EUR |
anti-GMP Synthase |
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YF-PA25201 | Abfrontier | 50 ul | 400.8 EUR |
anti-GMP Synthase |
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YF-PA15898 | Abfrontier | 50 ug | 435.6 EUR |
anti-GMP Synthase |
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YF-PA15899 | Abfrontier | 100 ug | 483.6 EUR |
Cyclic-di-GMP |
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B2045-1000 | Biovision | each | 666 EUR |
Cyclic-di-GMP |
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B2045-250 | Biovision | each | 248.4 EUR |
Cyclic GMP Standard, 125UL |
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C080-125UL | Arbor Assays | 125UL | 147.6 EUR |
Cyclic GMP Standard, 350UL |
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C080-350UL | Arbor Assays | 350UL | 272.4 EUR |
Cyclic GMP Standard, 625UL |
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C080-625UL | Arbor Assays | 625UL | 272.4 EUR |
Cyclic GMP Standard, 70UL |
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C080-70UL | Arbor Assays | 70UL | 147.6 EUR |
GMP-Fluorescein conjugate calibrator |
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13611 | AAT Bioquest | 100 nmol | 576 EUR |
IL-4 GMP, CF |
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PR15114CF | Neuromics | 50 ug | 1938 EUR |
IL-7 GMP, CF |
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PR15115CF | Neuromics | 25 ug | 2031.6 EUR |
IL-3 GMP, CF |
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PR15117CF | Neuromics | 50 ug | 1609.2 EUR |
IL-6 GMP, CF |
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PR15118CF | Neuromics | 50 ug | 2078.4 EUR |
IL-15 GMP, CF |
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PR15119CF | Neuromics | 5 ug | 606 EUR |
NT-3 GMP, CF |
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PR15120CF | Neuromics | 5 ug | 700.8 EUR |
Wnt-3a GMP, CF |
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PR15121CF | Neuromics | 10 ug | 778.8 EUR |
Activin A GMP, CF |
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PR15122CF | Neuromics | 50 ug | 1984.8 EUR |
IFN-gamma GMP, CF |
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PR15124CF | Neuromics | 100 ug | 1060.8 EUR |
TNF-alpha GMP, CF |
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PR15126CF | Neuromics | 100 ug | 1796.4 EUR |
Cyclic GMP EIA Kit |
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SKT-211-96 | Stressmarq | 1 plate of 96 wells | 568.8 EUR |
Anti-GMP Synthase (6B5) |
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YF-MA16544 | Abfrontier | 100 ug | 435.6 EUR |
Anti-GMP Synthase (1D10) |
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YF-MA11119 | Abfrontier | 100 ug | 435.6 EUR |
GMPS Antibody / GMP Synthase |
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RQ6255 | NSJ Bioreagents | 100 ug | 419 EUR |
IL4 Antibody |
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1-CSB-PA06737A0Rb | Cusabio |
|
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IL4 Antibody |
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1-CSB-PA004908 | Cusabio |
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IL4 Antibody |
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1-CSB-PA009551 | Cusabio |
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IL4 Antibody |
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1-CSB-PA009552 | Cusabio |
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IL4 Antibody |
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DF4713 | Affbiotech | 200ul | 420 EUR |
IL4 Antibody |
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AF5142 | Affbiotech | 200ul | 420 EUR |
IL4 siRNA |
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20-abx920531 | Abbexa |
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IL4 siRNA |
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20-abx920532 | Abbexa |
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IL4 Antibody |
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CSB-PA556277-100ul | Cusabio | 100ul | 379.2 EUR |
IL4 Antibody |
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1-CSB-PA011659LA01DO | Cusabio |
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IL4 Antibody |
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1-CSB-PA011659YA01HU | Cusabio |
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IL4 antibody |
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70R-49908 | Fitzgerald | 100 ul | 292.8 EUR |
IL4 antibody |
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70R-49909 | Fitzgerald | 100 ul | 292.8 EUR |
IL4 antibody |
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70R-49910 | Fitzgerald | 100 ul | 292.8 EUR |
IL4 antibody |
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70R-IR073 | Fitzgerald | 50 ug | 327.6 EUR |
IL4 antibody |
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70R-6231 | Fitzgerald | 50 ug | 560.4 EUR |
IL4 antibody |
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70R-6232 | Fitzgerald | 50 ug | 560.4 EUR |
IL4 Antibody |
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49540-100ul | SAB | 100ul | 399.6 EUR |
IL4 Antibody |
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49540-50ul | SAB | 50ul | 286.8 EUR |
IL4 antibody |
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70R-12277 | Fitzgerald | 200 ug | 603.6 EUR |
IL4 antibody |
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70R-14068 | Fitzgerald | 100 ug | 386.4 EUR |
IL4 antibody |
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70R-14286 | Fitzgerald | 100 ug | 386.4 EUR |
IL4 antibody |
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70R-15360 | Fitzgerald | 100 ug | 392.4 EUR |
IL4 antibody |
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70-IR07 | Fitzgerald | 50 ug | 357.6 EUR |
IL4 antibody |
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70-IR21 | Fitzgerald | 50 ug | 392.4 EUR |
IL4 antibody |
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70R-13672 | Fitzgerald | 100 ug | 438 EUR |
IL4 antibody |
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70R-13965 | Fitzgerald | 100 ug | 386.4 EUR |
IL4 protein |
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30R-2161 | Fitzgerald | 25 ug | 742.8 EUR |
IL4 protein |
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30R-2245 | Fitzgerald | 100 ug | 1585.2 EUR |
IL4 protein |
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30R-2486 | Fitzgerald | 10 ug | 422.4 EUR |
IL4 protein |
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30R-2487 | Fitzgerald | 10 ug | 390 EUR |
IL4 protein |
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30R-2488 | Fitzgerald | 10 ug | 390 EUR |
IL4 protein |
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30R-AI026 | Fitzgerald | 5 ug | 159.6 EUR |
IL4 Antibody |
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35227-100ul | SAB | 100ul | 302.4 EUR |
IL4 Antibody |
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35227-50ul | SAB | 50ul | 224.4 EUR |
IL4 antibody |
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10R-6628 | Fitzgerald | 50 ug | 198 EUR |
IL4 antibody |
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10R-6629 | Fitzgerald | 50 ug | 198 EUR |
IL4 antibody |
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10R-7718 | Fitzgerald | 500 ug | 678 EUR |
IL4 antibody |
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10R-7719 | Fitzgerald | 500 ug | 678 EUR |
IL4 antibody |
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10-I74A | Fitzgerald | 250 ug | 357.6 EUR |
IL4 antibody |
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10-I74B | Fitzgerald | 250 ug | 296.4 EUR |
IL4 Antibody |
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ABD4713 | Lifescience Market | 100 ug | 525.6 EUR |
IL4 siRNA |
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20-abx902667 | Abbexa |
|
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anti-IL4 |
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YF-PA23977 | Abfrontier | 50 ul | 400.8 EUR |
anti-IL4 |
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YF-PA12678 | Abfrontier | 50 ul | 435.6 EUR |
IL4 Antibody |
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R30494 | NSJ Bioreagents | 100 ug | 419 EUR |
IL4 Antibody |
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CSB-PA556277- | Cusabio | each | 402 EUR |
sP-Selectin/GMP-140/CD62P/ Rat sP- Selectin/ GMP- 140/ CD62P ELI |
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ELA-E0569r | Lifescience Market | 96 Tests | 1063.2 EUR |
Human GMP reductase 2 (GMPR2) |
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1-CSB-EP873740HU | Cusabio |
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Human GMP reductase 1 (GMPR) |
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1-CSB-EP339756HU | Cusabio |
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Mouse GMP-140 ELISA Kit |
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EMG0345 | Abclonal | 96Tests | 625.2 EUR |
Human GMP-140 ELISA Kit |
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EHG0345 | Abclonal | 96Tests | 625.2 EUR |
Rat GMP-140 ELISA Kit |
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ERG0345 | Abclonal | 96Tests | 625.2 EUR |
Rabbit GMP-140 ELISA Kit |
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ERTG0345 | Abclonal | 96Tests | 625.2 EUR |
Porcine GMP-140 ELISA Kit |
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EPG0345 | Abclonal | 96Tests | 625.2 EUR |
Immunoassay involves a large panel of monoclonal antibodies to characterize lymphocyte phenotype, cell proliferation with mitogen and antigens (tetanus toxoid; GMP C. Albicans, p24 and HIV gp160), HIV-specific cytotoxicity (env and gag), and rate of spontaneous cell mortality. Lymphocyte culture supernatants (stimulated with PHA) are collected to measure cytokines (IL2; IL4 ; IL10; gamma IFN) and T cell clones grown to characterize cytokine phenotype and pattern. Here we provide only a summary of the immunological data collected.