Thirty years of ups and downs in the "past and present" of stem cell therapy

Recently, the world’s top pharmaceutical company Vertex released the latest clinical trial data on the treatment of type I diabetes with VX-880 allogeneic stem cell therapy.
On the 90th day after receiving VX-880 treatment, the patient’s insulin production function was restored , The daily insulin requirement is reduced by 91%, while blood glucose control is significantly improved, and the tolerance is good.
This is the first proof that stem cell therapy can restore the function of islet cells in patients with type 1 diabetes
.

This new clinical research result has reignited people's expectations for stem cell therapy.
In the face of the current situation where no stem cell therapy has been approved by the FDA, can Forte Pharmaceuticals take the lead in the field of stem cells? Can stem cell therapy really be used by humans and benefit more patients?

Vertex announces data from the first patient in the Phase 1/2 clinical trial

"Born" with a halo—carrying unlimited hope

"Born" with a halo—carrying unlimited hope

Stem cells are a type of cell population with the potential for self-renewal and multi-directional differentiation.
They are mainly derived from cord blood, bone marrow, peripheral blood, embryos and dental pulp, etc.
They can be further differentiated into various types of cells to form various complex tissues of the body And organs
.

Since hematopoietic stem cells were used in the first bone marrow transplantation operation in 1968, the application of stem cell medical technology began to develop rapidly.
In 1998, American scientists discovered human embryonic stem cells (ES) that can be isolated and cultured in vitro, but there are ethical issues.
It was once questioned.
In 1999, stem cell therapy was listed by Science as the top ten scientific achievements because of its bright therapeutic prospects.
Then in 2006, Professor Shinya Yamanaka from Kyoto University in Japan obtained induced pluripotent stem cells (iPSC) through genetic technology for the first time.
), not only expected to avoid ethical issues, but also won the Nobel Prize for it
.

Since then, stem cells have gradually become a hot spot in the field of biomedicine.
Numerous scientists at home and abroad are scrambling to study the physiological mechanism and application prospects of stem cells in various fields of medicine
.

Simple schematic diagram of stem cell therapy

At present, stem cells are divided into embryonic stem cells, adult stem cells and iPS stem cells
.

Among them, embryonic stem cells are derived from early embryos and have strong value-added and differentiation capabilities.

Adult stem cells are relatively easy to obtain, there are no ethical issues, no histocompatibility, and theoretically, the risk of tumorigenesis is very low
.

However, the isolation and in vitro culture of adult stem cells have not yet been fully resolved.

Since the discovery of iPS stem cells, due to its unique advantages in stem cells, it has immediately become a research hotspot in the field of stem cells
.

Although the iPS stem cells generated after gene reprogramming avoids ethical problems and does not have histocompatibility problems, the reprogramming efficiency is low and there is the possibility of inducing mutations, which is still a problem that plagues scientists

Judging from the status quo, stem cell therapy technology is immature, but due to its multiple biological characteristics such as self-renewal ability, multi-directional differentiation potential and high proliferation ability, people have placed extremely high expectations for treatment and are already in metabolic diseases.
, Immune system diseases, cranial nerve diseases, neurodegenerative diseases, malignant tumors, digestive organ diseases and other disease fields have initiated clinical research
.

Disorderly "God Creation Movement"

Disorderly "God Creation Movement"

Although the “omnipotence” of stem cells has driven the tireless research of the scientific and pharmaceutical circles, it has also become a gimmick for bad businesses and companies to make money
.

Once in China, the scam of "100 thousand yuan a shot of stem cell injection" and the proliferation of so-called stem cell treatment centers from tertiary hospitals to beauty salons and small clinics have made people lose confidence in stem cell therapy

The top international journal Nature has twice reported on the disorder of stem cells in China.
Three months after the Ministry of Health of China stepped up its efforts to ban the clinical use of unapproved stem cell therapy, an investigation revealed that some domestic enterprises or clinics still After charging patients thousands of dollars in treatment fees, these clinics promote the treatment of serious diseases such as Parkinson's disease, diabetes and autism on their websites, and attract thousands of overseas medical tourists
.

DOI: https://doi.
org/10.
1038/484149a

Even in 2012, Feng Shiliang, member of the National Committee of the Chinese People’s Political Consultative Conference and director of the Liaoning Provincial Diabetes Treatment Center, cited a poem to describe the management problems of the stem cell industry in a proposal made by the National People’s Congress and the National People’s Congress: Close your eyes and'do not let you do it', the drug regulatory department is staring at the United States and'watching it'.
Scholars and experts advocate the belief in'doing boldly'.
The beauty agency said nonsense about “flickering”, and tens of thousands of patients were treated as guinea pigs
.

”

So far, the Ministry of Health and the State Food and Drug Administration have changed the standardization of stem cell drug research and development to a complete stop.
The 10 new stem cell drug registration applications accepted by the National Food and Drug Administration between 2004 and 2012 have all been cleared, and the development of stem cell drugs has returned to the original point
.

Restarting a new life-the third revolution in human medical history

Restarting a new life-the third revolution in human medical history

Even if there are chaos, it still cannot stop people’s enthusiasm for stem cell therapy.
In addition to the introduction of norms and regulatory policies, since 2015, various national ministries and commissions have successively issued a series of policies and technical guidance to support the development and transformation of stem cell technology.
The document aims to promote the research and development and clinical transformation of stem cell technology
.

In 2015, my country's first regulatory document for the management of stem cell clinical research, "Notice on Carrying out the Filing of Stem Cell Clinical Research Institutions" was released;

In 2017, the National Development and Reform Commission issued the "Thirteenth Five-Year" Biological Industry Development Plan, which pointed out the need to develop biotherapeutic products such as stem cells and CAR-T cell immunotherapy; at the same time, the "Thirteenth Five-Year" Special Plan for Health and Health Technology Innovation It clearly requires the strengthening of research on key technologies such as stem cells and regenerative medicine, immunotherapy, gene therapy, and cell therapy;

In 2018, the State Intellectual Property Office issued the "Catalogue of Key Intellectual Property Support Industries (2018 Edition)", which clearly listed stem cells and regenerative medicine, immunotherapy, cell therapy, etc.
as one of the key industries for national development and urgent need for intellectual property support.
one;

In 2020, the Ministry of Science and Technology issued the "Notice of the Ministry of Science and Technology on the Release of the National Key R&D Program "Stem Cell and Transformation Research" and other key special projects in 2020 application guidelines", with a total national funding of 240 million yuan
.

At the same time, the Drug Evaluation Center of the State Drug Administration organized the drafting of the "Technical Guidelines for Clinical Trials of Human-derived Stem Cells and Derived Cell Therapeutics (Draft for Comment)", with a view to providing applicants for drug R&D registration and conducting drug clinical trials.

With policy support, stem cell research has shown bright prospects, and its related clinical trials have sprung up like mushrooms
.

According to the data on the current status of domestic stem cell clinical research and development in 2021 compiled by Hans, China has already had 18 new stem cell drug applications for clinical approval, and 129 stem cell clinical research filing institutions have been approved in China, and the stem cell clinical trials have passed the approval filing.

Among them, Tianjin Angsai has been engaged in the research and development of stem cell drugs since its establishment in 2004.
Its mesenchymal stem cells for injection for the treatment of acute respiratory distress syndrome and chronic acute (subacute) liver failure have entered the IND stage; in addition, A total of 6 new stem cell drug clinical trials have been approved by Hans Group.
One of the new drug "Highly Active Human Umbilical Cord Mesenchymal Stem Cell Injection" Phase I/IIa clinical trial has been approved by the French Food and Drug Administration (ANSM) for treatment" Severe lower limb ischemia"; and the "human dental pulp mesenchymal stem cell injection" declared by Beijing Sanli Heze Biotechnology Co.
, Ltd.
for the treatment of periodontitis has also obtained the implied license of CDE clinical trial.
It can be seen that the domestic stem cell therapy is positive Step forward and develop rapidly
.

Globally, as of September 2020, more than 8,100 stem cell-related clinical studies have been registered on the US ClinicalTrials website, including 4,026 cases in the United States, 1923 cases in Europe, and 657 cases in China, second only to the United States and European countries
.

In foreign countries, according to incomplete statistics, 18 stem cell therapies have been approved for marketing, and 10 of them meet the definition of drugs

18 stem cell therapy products approved for marketing (photo source: National Health Products)

At present, stem cell therapy is constantly being standardized, and its research results are moving towards a bright future.

Reference materials:

Reference materials:

[1]https:// [2]https://baijiahao.
baidu.
com/s?id=1618737996109128231&wfr=spider&for=pc

[2]https://baijiahao.
baidu.
com/s?id=1618737996109128231&wfr=spider&for=pc

[3]https:// [4]https:// [5]https://mp.
weixin.
qq.
com/s/MEwaUUskDKM669z-fo9yqQ

[5]https://mp.
weixin.
qq.
com/s/MEwaUUskDKM669z-fo9yqQ