Latest research! Hematopoietic stem cell transplantation may provide up to 10 years of disease exemption for MS patients

The research was published in the online journal Neurology on January 20, 2021, which is the medical journal of the American Academy of Neurology. MINNEAPOLIS-A new study shows that hematopoietic stem cell transplantation after strong immunosuppression can prevent 71% of people with relapsing-remitting MS from multiple sclerosis (MS) for up to 10 years after treatment His disability worsened. The study also found that in some people, their disability improved after 10 years of treatment. In addition, more than half of patients with advanced secondary MS have no symptoms worsening 10 years after transplantation.

Although most patients with MS are first diagnosed as relapsing-remitting MS, their symptoms are first onset and then in remission, but many patients with relapsing-remitting MS will eventually change to secondary progressive MS without significant fluctuations in symptoms. Instead, the disease is slow and continues to deteriorate.

The research involves autologous hematopoietic stem cell transplantation, which uses healthy blood stem cells in the participant's own body to replace diseased cells.

Dr. Matilde Inglese, MD, University of Genoa, Italy, said: "So far, conventional treatment has prevented MS patients from suffering more attacks and symptoms, but in the long run it has not." Academician of the American Academy of Neurosciences. "Previous research has shown that more than half of MS patients who take medication for the disease will still get worse within 10 years. Our results are exciting because they show that hematopoietic stem cell transplantation may prevent someone's MS disability from getting worse in the long term. Terminology. "

The study investigated 210 MS patients who received stem cell transplants from 1997 to 2019. Their average age was 35 years. Among them, 122 cases had relapsing-remitting MS, 86 cases had secondary progressive MS, and two had primary progressive MS.

The researchers evaluated the participants six months, five years and ten years after transplantation.

This study was conducted for five years, and the researchers found that 80% of people had no worsening of MS disability. By the 10-year mark, 66% of people still have not experienced the deterioration of their disability.

Researchers only studied people with the most common MS and found that 86% of them did not experience deterioration in disability five years after transplantation. Ten years later, 71% of disabled people have not deteriorated.

Similarly, patients with progressive MS also benefit from stem cell transplantation. Researchers found that 71% of patients with this type of MS did not experience worsening disability five years after transplantation. Ten years later, 57% of disabled people have not deteriorated.

Ingles said: "Our research shows that strong immunosuppression and hematopoietic stem cell transplantation should be regarded as a treatment for MS patients, especially those who do not respond to conventional therapies."

Hematopoietic stem cell expansion, transfection and gene editing optimization solutions

Bill Gates once predicted that what can surpass Microsoft in the future must appear in the field of biomedicine. And if you want to ask what biomedical technology is the hottest in recent years, then stem cell technology is definitely one of the answers you get.

Hello everyone, I am Sansan, and I am very happy to meet you again on ZePingBIO. Today we are discussing with you a special kind of stem cells- hematopoietic stem cells . Hematopoietic stem cells (HSC), also known as pluripotent stem cells, are the ancestors of various blood cells and immune cells.

Of course, when talking about hematopoietic stem cells, first of all we have to thank the three scientists Ernest A. McCulloch, James E. Till and Siminovitch from the University of Toronto in Canada. In 1961, Till and McCulloch published their initial observations in the journal Radiation Research in obscurity, opening the door to stem cell research for us ever since. In 1961 , Till's postdoctoral supervisor Siminovitch proposed the discovery of hematopoietic stem cells.

image

Ernest A. McCulloch 与 James E. Till

Today, hematopoietic stem cells (HSC) are widely used in transplantation and clinical treatment. Combining the advancement of gene therapy and gene editing technology, the research of gene therapy based on hematopoietic stem cells to treat various blood diseases and immune diseases Much progress has been made in recent years. However, the commonly used clinical sources of HSC are bone marrow, mobilized peripheral blood and umbilical cord blood. Due to the low content of HSC in these tissues and the scarcity of histocompatibility antigen-specific donors, many patients cannot obtain a sufficient amount of histocompatibility matching HSC.

Therefore, in all cell therapy products, obtaining high-yield, high-quality and effective effector cells is the key to clinical treatment. The same is true for gene-edited CD34+ hematopoietic stem cell therapy.

So, how to solve these problems of hematopoietic stem cells ? Don’t worry, Sansan will bring you a complete set of hematopoietic stem cell optimization solutions today. Please review:

 

Hematopoietic stem cell supply plan

 

As we all know, human cord blood CD34+ cells contain hematopoietic stem cells and progenitor cells. Compared with other human tissue-derived hematopoietic stem cells, cord blood CD34+ hematopoietic stem cells are more naive and can avoid donor and recipient HLA (Human Leukocyte Antigen). The problem of matching is an ideal model for transplantation, autoimmune diseases, and stem cell research. The LONZA primary cell product represented by ZePingBio has a rich source of donors. The cryopreserved CD34+ hematopoietic stem cells of human cord blood are obtained from cord blood mononuclear cells (MNCs) from a single healthy donor through positive immunomagnetic separation and expressed by CD34+ Verification can guarantee the purity ≥90%. All of its cells do not contain HIV-1 and hepatitis B, and each batch of cells can provide a quality analysis report. Each branch contains ≥1,000,000 cells.

 

Item No.

description

specification

2M-101

CD34+ hematopoietic stem cells from bone marrow

≥100,000 cells

2M-101A

CD34+ hematopoietic stem cells from bone marrow

≥300,000 cells

2M-101B

CD34+ hematopoietic stem cells from bone marrow

≥500,000 cells

2M-101C

CD34+ hematopoietic stem cells from bone marrow

≥1 million cells

2M-101D

CD34+ hematopoietic stem cells from bone marrow

≥2 million cells

2C-101

CD34+ hematopoietic stem cells from cord blood

≥1 million cells

2C-101A

CD34+ hematopoietic stem cells from cord blood

≥500 000 cells

4Y-101C

Human CD34+ hematopoietic stem cell separation automates peripheral blood (using immunomagnetic bead positive sorting)

≥1 million cells

4Y-101D

Human CD34+ hematopoietic stem cell separation automates peripheral blood (using immunomagnetic bead positive sorting)

≥5 million cells

4Y-101E

Human CD34+ hematopoietic stem cell separation automates peripheral blood (using immunomagnetic bead positive sorting)

≥10 million cells

4Y-101F

Human CD34+ hematopoietic stem cell separation automates peripheral blood (using immunomagnetic bead positive sorting)

≥25 million cells

In addition, Beijing Zeping is the agent of LONZA bone marrow CD34+ cells. The donors are abundant. Whether it is a study that requires a large number of cells from a single donor, or the study of the differences between donor cells of different ages, genders, and races, they can obtain ideal Cell products.

Hematopoietic stem cell culture expansion solution

Everyone knows that there are many factors that affect the in vitro expansion of cord blood CD+34 cells. Throughout recent years, basic research results have found a series of culture systems and additives that help expand HSC, such as cytokines (SCF , TPO, FLT-3L, IL-3, IL-6, G-CSF, etc.), co-culture with stromal cells, and add some small molecules (prostaglandin E2), or further purify cord blood stem cells to obtain In vitro expansion, but the HSC obtained by these methods still cannot meet clinical needs. LONZA, an agent of ZePingBio, recommends using its star product X-VIVO series serum-free medium as an alternative medium to cultivate hematopoietic stem cells. Among them, the X-VIVO 15 series supports the proliferation of a variety of cells including hematopoietic stem cells, monocytes, macrophages, lymphocytes, etc.

CD34+ hematopoietic stem cells derived from human cord blood were cultured in X-VIVO 15 containing rec human TPO (25ng/mL), Rlt3 ligand (25ng/mL), and SCF (13ng/mL). Pre-coated fibronectin. Use Nanolive's 3D Cell Explorer for 15h live cell imaging (3 images per minute).

 

Item No.

description

specification

04-418Q

X-VIVO 15 immune cell culture medium, RUO

1L

BEBP02-054Q

TheraPEAK X-VIVO 15 immune cell culture medium, GMP

1L

BE08-879H

TheraPEAK X-VIVO 15 immune cell culture medium, GMP

5l

 

Hematopoietic stem cell culture expansion solution

Primitive hematopoietic stem cells can regenerate the entire hematopoietic system and immune system due to their totipotency. They are ideal target cells for gene therapy. As far as Sansanzui learned, the current main transfection methods for hematopoietic stem cells are: adenovirus transfection, retrovirus and lentivirus transfection, transposon and artificial chromosome transfection. Today, Sansan recommends a 4D Nucleofector nuclear transfer system that has been maturely used in CAR-T cell research and can efficiently transfect hematopoietic stem cells.

image

4D Nucleofector nuclear transfer instrument system ( poke me for technical details )

 

It is worth mentioning that the 4D Nucleofector nuclear transfection system is not only easy to operate, but also supports large-scale hematopoietic stem cell transfection production. The transfection efficiency of most cell lines can be as high as 50-70%. Some primary cells are transfected. The dyeing efficiency can exceed 90%.

 

Item No.

description

specification

AAF-1002B

4D Nucleofector Core unit

1/pkg

AAF-1002X

4D Nucleofector X unit

1/pkg

AAF-1002L

4D Nucleofector LV unit

1/pkg

 

Hematopoietic stem cell gene editing solution

We all know that hematopoietic stem cells have the potential to self-renew and differentiate into various types of blood cells, and have been considered as one of the most ideal target cells for gene therapy. In recent years, gene therapy of hematopoietic stem cells based on lentiviral vectors has gradually entered the clinic. At the same time, with the continuous development of gene editing technologies such as CRISPR-Cas9, the research on precision gene therapy of second-generation hematopoietic stem cells has made important progress. ZePing is the agent of CRISPR gene editing products of IDT (Integrated DNA Technologies), an internationally renowned CRISPR technology service provider. It can support research on gene editing of hematopoietic stem cells.

image

IDT Alt-R® CRISPR/Cas9 experiment process ( poke me for technical details )

 

Item No.

product

specification

 

Alt-R®CRISPR-Cas9 crRNA

10 nmol

 

Alt-R®CRISPR-Cas9 crRNA XT

10 nmol

1072534

Alt-R®CRISPR-Cas9 tracrRNA

100 nmol

1075927

Alt-R®CRISPR-Cas9 tracrRNA , ATTO ™ 550

5 nmol

 

Alt-R®CRISPR-Cas9 sgRNA

10 nmol

 

References (swipe up and down to view)

 

1 Wang L, Gu ZY, Liu SF, et al. Single-versus Double-Unit umbilical cord blood transplantation for hematologic diseases: a systematic review[J]. Transfus Med Rev, 2019, 33(1):51-60.

 

2 Pineault N, Abu-Khader A. Advances in umbilical cord blood stem cell expansion and clinical translation[J]. Exp Hematol, 2015, 43(7):498513.

 

3 Pineault N, Cortin V, Boyer L, et al. Individual and synergistic cytokine effects controlling the expansion of cord blood CD34+ cells and megakaryocyte progenitors in culture[J]. Cytotherapy, 2011, 13(4): 467-480.

 

4 Codispoti B, Rinaldo N, Chiarella E, et al. Recombinant TATBMI-1 fusion protein induces ex vivo expansion of human umbilical cord blood-derived hematopoietic stem cells[J]. Oncotarget, 2017,
8(27):43782-43798.

 

5 Jiang MM, Chen HD, Lai SJ, et al. Maintenance of human haematopoietic stem and progenitor cells in vitro using a chemical cocktail[J]. Cell Discov, 2018, 4:59.

 

6 Boitano AE, Wang J, Romeo R, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells[J]. Science, 2010, 329(5997):1345-1348.

 

7 Fares I, Chagraoui J, Gareau Y, et al. Pyrimidoindole derivatives are agonists of human hematopoietic stem cell self-renewal[J]. Science, 2014, 345(623):1509-1512.

 

8 Xu Shiqi, Ding Yahui, Zhang Yu, et al. The mechanism of UM171 expansion of cord blood hematopoietic stem cells in vitro[J]. Chinese Tissue Engineering Research, 2018, 22(21):3328-3334.

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Origin blog.csdn.net/Bio12345/article/details/112966343