In the search engine, type the words "stem cell", "umbilical cord blood" and "placenta storage". The returned results are all question marks: Is stem cell therapy reliable? Is cord blood necessary to save? Is the child's placenta useful? And so on.

Release date: 2014-12-17

In the search engine, type the words "stem cell", "umbilical cord blood" and "placenta storage". The returned results are all question marks: Is stem cell therapy reliable? Is cord blood necessary to save? Is the child's placenta useful? And so on.

Today, more and more people know the term "stem cell", and more and more people are paying attention to the clinical application of "stem cell". The reason is that people feel vaguely that stem cells "can save lives."

Stem cells can really save lives. Han Zhongchao, director of the National Stem Cell Engineering Technology Research Center and professor of the Institute of Hematology at the Chinese Academy of Medical Sciences, shared a short story at the first "Stem Cell Media Salon" organized by the Chinese Journal of Science and Technology: after the nuclear accident at the Fukushima nuclear power plant in Japan in 2011, the nuclear power plant All staff members were asked to take some of their own stem cells in advance and store them in their own stem cells in case of a nuclear leak.

However, although the clinical application of stem cell technology represents a major direction of medical development, it also contains the hope of curing a variety of incurable diseases. However, in recent years, stem cells have gone from the laboratory to the "last mile" of clinical application. Not smooth. Among them, the umbilical cord blood storage is frequently questioned, and the "perinatal stem cells" that scientists have high hopes for are incapable of exerting difficulties.

Short board for cord blood storage

In April of this year, Shanghai Business Daily reported that an 8-month-old leukemia baby could not use autologous cord blood, which cast a shadow on the storage of autologous cord blood. Experts explained that children under the age of 1 suffering from leukemia, "generally presumed to be congenital", in this case, the use of autologous cord blood stem cells is generally not recommended.

This statement was confirmed by Professor Xiao Xiaofan, professor of pediatrics at the Institute of Hematology, Chinese Academy of Medical Sciences and director of the Children's Hematology Clinic. She pointed out that autologous cord blood hematopoietic stem cell transplantation does have a self-help effect, but it has certain indications as other treatment methods. It is not suitable for the treatment of any disease. If "the cord blood itself has problems", then for this congenital disease The cord blood is "not available".

Qian Linsheng, a well-known blood disease expert and professor of the Institute of Hematology at the Chinese Academy of Medical Sciences, once said that in the field of pediatric hematology, autologous cord blood storage is available as a treatment method, but it is not widely used clinically. To one hundred thousandth."

Han Zhongchao gave specific figures: At present, China's cord blood storage is close to 500,000, but no more than 10 cases are actually used for the treatment of autologous diseases.

The self-utilization rate of cord blood is so low. The congenital genetic cause (the cord blood bank needs to consult the family genetic history when storing cord blood) is only a small aspect. The reason why cord blood cannot be widely used is more important because it is in the cord blood. The number of stem cells is too small and can only be used by children under 30 kg. If it exceeds this range, "the treatment effect will be very poor."

The internationally accepted standard is that the number of umbilical cord blood nucleated stem cells can reach at least 2.0×107 to correspond to people weighing about 1 kg, while the number of nucleated cells stored in disposable umbilical cord blood is generally around 3.0×108 or even lower. For adults, the amount is obviously not enough.

"Generally, the doctor will not use cord blood as the first choice, but use peripheral blood, parental bone marrow-derived stem cells (for transplant treatment)." Han Zhongchao said that the number of hematopoietic stem cells in cord blood "limits it can not be used for many Treatment of the disease."

In theory, the number of umbilical cord blood hematopoietic stem cells can be amplified by artificial techniques. However, artificial amplification requires both an increase in the number of stem cells and a non-differentiation into functional cells, which is difficult and has not been reported to be mature. Amplification technology of human stem cells.

Mesenchymal stem cells ignite new hope

Yan Xiaofan said that hematopoietic stem cell transplantation therapy has a good therapeutic effect on some diseases such as leukemia and aplastic anemia. Moreover, since hematopoietic stem cells are the earliest stem cells that Chinese people "know", they are highly regarded in people's minds. As people discovered that cord blood also contains hematopoietic stem cells, the world's first cord blood hematopoietic stem cell bank was soon built. By the year 2000, several cord blood hematopoietic stem cell banks were also established in China.

The value of storing cord blood is that it is a source of hematopoietic stem cells. However, people quickly discovered a short plate of hematopoietic stem cells in cord blood. Until the study of the development process and regulation mechanism of hematopoietic stem cells, domestic scholars first discovered that the original placental tissue also contains a large number of hematopoietic stem cells, and agreed that the placenta is a new source of hematopoietic stem cells for clinical transplantation.

As the earliest and most used stem cell found in humans (from the first bone marrow transplant in Thomas in 1956 and the success of hematopoietic stem cells, the hematopoietic stem cells have been nearly 60 years old), hematopoietic stem cells have always been the most abundant adult stem cells. A well-known representative. However, stem cells that have been circulated in recent years to "cure all diseases" are not hematopoietic stem cells. "Who" has the ability to steal the "wind" of hematopoietic stem cells?

It is called mesenchymal stem cells. "Now the stem cell chaos, 'this can cure it can also cure', mainly said stem cells." Han Zhongchao said that in the 1990s, scientists first discovered mesenchymal stem cells in human bone marrow. The current research shows that this type of stem cells is almost present in all tissues and organs of humans. "Especially, when the child is born, the mesenchymal stem cells of the fetal accessory tissues (placenta, amnion, umbilical cord, etc., also known as perinatal tissue) Very rich, low in immunogenicity, is something that hopes to turn waste into treasure."

"Mesenchymal stem cells are stem cells that are widely used worldwide after hematopoietic stem cells." Chen Hu, director of the Center for Cell and Gene Therapy of the Academy of Military Medical Sciences and director of the Institute of Hematopoietic Stem Cell Research, at the "Stem Cell Media Salon" It is said that due to the multi-directional differentiation ability of mesenchymal stem cells, it can be induced into adipocytes, bone cells, chondrocytes, cardiomyocytes, nerve cells, etc. in vitro. If the tissues and organs need to be repaired, the mesenchyme can be used. Stem cells differentiated from tissue cells to replace them.

Chen Hu explained that the role of mesenchymal stem cell tissue repair is mainly reflected in three aspects, in addition to the substitution effect, it also has a "paracrine effect", that is, the secretion of many cytokines (mainly including anti-withering molecules, immunity Regulatory molecules, anti-scarring molecules, supporting molecules, angiogenic molecules, chemotactic molecules 6 categories), these factors can participate in the repair of tissues; in addition, mesenchymal stem cells can also inhibit rejection, play a role in immune regulation .

"We recently performed protein detection on 174 cytokines. Compared with umbilical cord mesenchymal stem cells and bone marrow mesenchymal stem cells, 101 of the cytokines were highly secreted and varied, of which 22 umbilical cord mesenchymal secretions. The amount is much higher than the bone marrow." Chen Hu said.

It is clear to those who know about stem cell transplantation that a graft-versus-host disease (GVHD), a rejection reaction, occurs during allogeneic transplantation. If the rejection is "severe", the patient is likely to die within 30 days.

"We found that mesenchymal stem cells can induce immune tolerance, which can reduce rejection." Chen Hu shared, "We are the first in the world to use the donor's umbilical cord mesenchymal stem cells for joint transplantation and found Acute GVHD can be reduced from 53.3% to 11.1%, and chronic GVHD can be reduced from 28.6% to 14.3%."

After the publication of the research results of Chen Hu et al., the Ministry of Health approved the clinical trial of the technology: “Agree to the 307th Hospital of your hospital to develop human umbilical cord mesenchymal stem cells for the treatment of graft-versus-host disease (GVHD). Clinical laboratory research." The paper also won "China's 100 most influential international academic papers."

Han Zhongchao compared the function of immune regulation of mesenchymal stem cells to the "community committee of the cell society", "using this feature can be used to treat many immune abnormal diseases, inflammatory reactions, etc." Chen Hu pointed out that mesenchymal stem cells currently have 130 indications. "That is to say, 130 diseases with ineffective or poorly treated drugs are expected to be treated by mesenchymal stem cells."

Mesenchymal stem cells also have great potential in the field of childhood disease applications. "A 2011 international umbilical cord (blood) mesenchymal stem cells for children's diseases concluded that mesenchymal stem cells play an important role in many pediatric diseases, including inflammation, tumors, and autoimmune diseases. Canada has approved the use of it as a new anti-GVHD drug." Xiao Xiaofan added, however, as a routine treatment of the disease, a standardized, large-sample clinical trial is needed to support the above theory.

Perinatal stem cell technology

"In neonatal perinatal tissues, both mesenchymal stem cells and hematopoietic stem cells are very rich in content, and the perinatal stem cell proliferation and differentiation ability is much stronger than the bone marrow and blood stem cells in humans after birth, and the immunogenicity is relatively low. "Han Zhongchao has several significant advantages in perinatal stem cells when he interacts with the media: clinical perinatal stem cells are ethical, low tumorigenicity after transplantation, and can be turned into waste. It can be said to be safe. Also practical.

"Perinatal stem cell technology is bound to bring new applications." Han Zhongchao said, "We are the first in the world to use placenta-derived stem cells to effectively treat type 2 diabetes (adult-onset diabetes). The results of this clinical trial have been published. Mesenchymal stem cells co-transplanted with other cells to treat 21 patients with severe aplastic anemia also achieved good results (published)."

In addition, in the field of tissue engineering, placenta-derived stem cells are also particularly suitable for 3D bioprinting technology. "Using digestible biomaterials, together with stem cells, can be formed in different environments, such as the liver and kidneys. Science has published articles that some organizations have been able to breed." Han Zhongchao said.

At present, China's research in the field of stem cell technology is second only to the United States, and it is in the world's leading position in the research of bone marrow, umbilical cord, and placenta mesenchymal stem cells. It has pioneered the umbilical cord library and placenta library worldwide. However, unfortunately, due to the uncertain policies and regulations in this field in China, the country has not yet approved a new stem cell drug in the clinic. In South Korea, due to the strong policy support, the number of approved new stem cell drugs has reached 3, It is equal in number to the United States; Canada (New Zealand) and Australia each have a stem cell drug that is approved for marketing.

Law expert and senior consultant of Republic Law Firm Zhang Jianzhong is very concerned about the legal risks and legislative norms in the field of stem cells. He said in the "Stem Cell Media Salon" that the legislation on the clinical application of stem cell technology in different countries is divided into three categories. Some Catholic countries in Europe such as Austria, Ireland, Poland, Norway, etc. only take strict research on stem cells. Forbidden attitudes; Germany, the United States, Italy and other countries adopt a cautious and restrictive attitude toward stem cell research and application. More representatively, US President Barack Obama "released the ban" of stem cell research and gave support when he took office. Countries with flexible support attitudes represented by South Korea, including China.

"But China still lags behind in the legislative norms, which is also determined by the nature of the law." Zhang Jianzhong believes that policy is the basis for formulating laws. However, China’s policy on stem cell medical care has not yet reached the level of legislation of the National People’s Congress. Whether support and encouragement are irrelevant, but related to factors such as “chaotic market” “requiring a high-quality regulation” and “public perception”.

"We use stem cells to do clinical trials of many diseases, and we are not all very clear (therapeutic), but we have seen that stem cell technology is helpful in treating these diseases that threaten humans. This is the progress of civilization and should be supported." When the tiger talked about this, the attitude was very serious. "The rejection reaction is very serious. Compared with the death of the eyelid in 30 days, the mesenchymal stem cells can save 70% of the patients, and the longest is 4 years (survival). I think it should be approved for clinical applications."

"We don't want to speculate on stem cell technology, what kind of disease can be treated, whether it has this foundation, whether there is a theoretical basis, whether there is proof of practice, so it is better to evaluate it." Chen Hu said. At the same time, he also said that because stem cell products have the speciality of "ethnic" differentiation, they can restrict the entry of stem cell products from Europe and the United States into China. "We can wait for us. Otherwise, the research situation of Chinese stem cells will never be the case today. It’s coming out."

(Original title: Stem Cell Health: Why can't you take the last step?)

Source: Chinese Journal of Science

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