Stars in stem cells! Clinical research and application of umbilical cord mesenchymal stem cells

In recent years, the research on mesenchymal stem cells has been continuously increasing, and so far, more than 47000 articles related to mesenchymal stem cells have been retrieved on Pubmed.

Umbilical cord mesenchymal stem cells have always been regarded as treasures by scientists and are constantly demonstrating their potential for disease treatment and anti-aging.

Today, the editor will explain to you what umbilical cord mesenchymal stem cells are, and demonstrate the charm of umbilical cord mesenchymal stem cells in the medical field by introducing clinical research application cases of umbilical cord mesenchymal stem cells.

What are umbilical cord mesenchymal stem cells?

Umbilical cord mesenchymal stem cells (hUC MSCs) originate from the umbilical cord of newborns and are safer and more primitive compared to adult mesenchymal stem cells. They have stronger proliferation, differentiation, and immune regulatory abilities; In addition, compared to other sources of mesenchymal stem cells, umbilical cord mesenchymal stem cells are obtained from detached umbilical cord tissue without any harm to the human body. Therefore, umbilical cord MSCs are suitable for clinical research and application, and are the preferred choice for cell therapy and regenerative medicine.

Umbilical cord mesenchymal stem cells have shown high differentiation ability in vitro, including chondrocytes, adipocytes, osteoblasts, skeletal cells, cardiomyocytes, liver cells, as well as producing glucagon cells, somatostatin secreting cells, glial cells (oligodendrocytes), and dopaminergic neurons. Therefore, umbilical cord mesenchymal stem cells are very suitable for clinical applications and scientific research.

Mesenchymal stem cells have become a research hotspot

In recent years, the research on mesenchymal stem cells has been on the rise, and ClinicalTrials from NIH in the United States is the world's largest clinical research database. According to the search results of the database, as of May 13, 2019, there were 753 clinical studies registered in the database regarding mesenchymal stem cells. Among them, the number of clinical studies conducted in China, Europe, and the United States ranks among the top three in the world.

From the perspective of the types of diseases treated, clinical research on mesenchymal stem cells involves hundreds of diseases. Among them, neurological, cardiovascular, and orthopedic diseases are the three main research areas, accounting for more than 15%, and the total exceeds half. In addition, the proportion of diabetes, liver, lung, gastrointestinal tract, skin, autoimmune diseases and graft versus host disease (GVHD) is about 5%, which is an important clinical research direction of mesenchymal stem cells.

Clinical application research case of umbilical cord mesenchymal stem cells

01.Metabolic diseases

1.1 Diabetes

At present, there is no radical cure for diabetes clinically, and we can only rely on insulin or drugs in vitro to reduce blood sugar, and at the same time cooperate with diet and exercise. Mesenchymal stem cells have the ability to stimulate pancreatic islets β The function of cell regeneration.

In China, there are three top hospitals that have carried out clinical research on mesenchymal stem cell transplantation in the treatment of type II diabetes. Most patients have achieved the effect of reducing blood sugar and insulin, and some even stop taking medication. At the same time, the patient's physical condition has improved and their sub-health status has been corrected to a certain extent.

Fuzhou General Hospital of Nanjing Military Region explored the safety and efficacy of umbilical cord mesenchymal stem cells combined with autologous bone marrow mesenchymal stem cells in the treatment of type I diabetes without immunotherapy. The results showed that the treatment effect of 42 patients was good. C-Pep increased by 105.7%, insulin 49.3%, HbA1c decreased by 12.6%, fast blood glucose decreased by 24.4%, and insulin demand decreased by 29.2%.

1.2 Complications of diabetes

Mesenchymal stem cells have a broader application prospect in the complications of diabetes.

1.2.1 Diabetes foot

At the Shaanxi Provincial People's Hospital, under sterile conditions, umbilical cord mesenchymal stem cell suspension was injected into the muscles at intervals of 3cm x 3cm at the lesions of 5 inpatients with type II diabetes complicated with diabetic foot. For those with severe lesions, injections were spaced 1cm x 1cm apart in the foot, with a focus on injection around the ulcer. After treatment, the degree of foot pain and numbness was significantly reduced, intermittent claudication improved markedly, and ulcers completely healed.

At the Affiliated Anhui Provincial Hospital of Anhui Medical University, umbilical cord mesenchymal stem cells were injected into the ulcer sites of the affected limbs of 53 patients with grade II-IV diabetic foot. After three months of treatment, compared to the control group, the treatment group showed significant improvement in skin temperature, ankle-brachial pressure index, skin oxygen tension, and walking distance.

1.2.2 Diabetic nephropathy

The Clinical Medical College of Fuzhou General Hospital, Second Military Medical University, and the Affiliated Changzheng Hospital of the Second Military Medical University treated 15 patients with umbilical cord mesenchymal stem cells via intervention in the pancreatic dorsal artery, bilateral renal arteries, and peripheral vein infusion. After treatment, the patients showed improvements in blood pressure, blood sugar, C-peptide levels, and renal function indicators. In terms of clinical efficacy in improving diastolic blood pressure and renal function, the treatment group outperformed the control group treated with oral telmisartan plus subcutaneous insulin injection.

02.Neurological disorders

2.1 Parkinson's disease

The first case of stem cell transplantation for Parkinson's disease in China was completed at a hospital in Shijiazhuang. Xie Xiyun, a 76-year-old from Indonesia, had been suffering from Parkinson's disease for over a decade, experiencing stiffness and contraction in three fingers of his right hand, body rigidity, swallowing difficulties, and loss of self-care ability. Within hours of receiving mesenchymal stem cell transplantation, he was able to eat smoothly and comfortably watch television that evening, with significant improvement in other symptoms.

Dr. Sun Li from China Medical University infused suspension containing umbilical cord mesenchymal stem cells into the neck arteries of 10 Parkinson's disease patients. After transplantation, the patients showed improvements in walking posture, tremor severity, voluntary movement, and ability to sit and stand. Not only did it effectively control the progression of Parkinson's disease, but it also significantly improved the function of damaged brain tissue, thus enhancing the quality of life for the patients.

2.2 senile dementia

The team led by Zhou Qiang at Jinyang Hospital in Guiyang City treated four elderly dementia patients using autologous bone marrow stem cells. The first patient, a 75-year-old male, did not recognize family members upon admission and had loss of bladder and bowel control. Following the transplant treatment, these symptoms rapidly improved, and upon discharge, he not only recognized his family members but also regained normal bladder and bowel function.

2.3 Insomnia

Dr. Wang Yali from Zhejiang Armed Police Hospital treated 19 patients with insomnia by intravenous infusion of umbilical cord mesenchymal stem cells. These patients all experienced difficulty falling asleep, decreased sleep quality, and total sleep time of less than 6 hours. After one month of treatment, the improvement in sleep quality in patients was comparable to that of oral medication. After two months of treatment, patients' sleep quality scores were significantly better than those of oral medication. After three months of treatment, patients' sleep quality was also significantly better than that of oral medication, and the effects of a single treatment could last up to one year, significantly improving sleep quality in patients.

03.Musculoskeletal disorders

3.1 Degenerative joint disease

In the 1990s, Brittberg and others began to achieve certain results in repairing cartilage injuries using autologous chondrocytes. Therefore, more and more studies began to focus on mesenchymal stem cells. Mesenchymal stem cells can differentiate into various tissues and repair articular surface cartilage and subchondral bone injuries.

In a study conducted by Akgun et al. from the Department of Orthopedics and Traumatology at Istanbul University in Turkey, they compared the therapeutic effects of autologous bone marrow mesenchymal stem cells and chondrocytes in 14 patients with osteoarthritis. They found that patients receiving mesenchymal stem cell treatment showed more significant improvements in knee injury and osteoarthritis outcome scores (KOOS) and visual analog scale (VAS) scores.

Wakitani et al. from the Feinberg School of Medicine at Northwestern University and the Cleveland Clinic Hospital at Ohio University conducted a clinical trial using mesenchymal stem cells. In the experimental group, a collagen gel mixed with autologous bone marrow-derived mesenchymal stem cells was implanted into the patients' articular cartilage lesions, while the control group received only an equal amount of collagen gel. Both groups showed improvements in joint function, but only the experimental group showed regeneration of transparent cartilage at the site of injury. They followed up with 41 patients who received mesenchymal stem cell therapy for up to 11 years and found no serious complications.

04.Reproductive system diseases

4.1 Infertility

Repairing severe damage to the endometrium, which is the nightmare of many infertile women, is now possible through mesenchymal stem cell regenerative technology, bringing hope to fulfill women's dreams of motherhood.

Professor Hu Yali's team from the Obstetrics and Gynecology Department of Gulou Hospital in Nanjing, collaborating with Professor Dai Jianwu's team from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, successfully developed, for the first time internationally, a method to combine collagen scaffolds with mesenchymal stem cells. By integrating traditional hysteroscopic techniques, they achieved functional repair of damaged endometrium, helping three patients fulfill their dreams of becoming mothers.

Ms. Hu from Yancheng, Jiangsu, experienced three natural miscarriages between the ages of 31 and 34, leading to severe adhesions in her uterine cavity due to post-miscarriage uterine curettage surgeries. Utilizing mesenchymal stem cells, Gulou Hospital in Nanjing successfully repaired her endometrium over the course of eight months. This enabled her to conceive successfully, and on July 17, 2014, she gave birth to the first "regenerative medicine baby" in China.

Nanjing Gulou Hospital's mesenchymal stem cell "endometrial regeneration surgery" has successfully enabled 13 infertile patients with severe uterine cavity adhesions to conceive and give birth, resulting in a total of 14 healthy "regenerative medicine babies."

4.2 Premature ovarian failure

Premature ovarian failure refers to the phenomenon in which women experience ovarian atrophy and stop ovulating before the age of 40. Currently, about 1% of women of reproductive age worldwide experience premature ovarian failure, making it a significant cause of female infertility.

Professor Wu Ji and his team from Shanghai Jiao Tong University in China isolated female reproductive stem cells from one- to two-week-old green fluorescent protein transgenic mice. After purification, culture, and other processes, these cells were transplanted into mice with premature ovarian failure. The research results showed that female reproductive stem cells, like other stem cells, have homing properties. After homing, some cells differentiated and gradually developed into mature oocytes, thus restoring ovarian function.

4.3 Erectile dysfunction (ED)

Using stem cell therapy for erectile dysfunction can both replace damaged or dead penile tissue cells and secrete factors to repair functionally impaired penile tissue cells.

Fifteen erectile dysfunction patients in Denmark received mesenchymal stem cell infusions without medication or penile transplantation. After six months, eight men were able to engage in sexual intercourse normally.

05.Autoimmune diseases

In 2007, Professor Sun Lingyun in China successfully treated two cases of refractory systemic lupus erythematosus using mesenchymal stem cells, and the following year, he treated nine more cases. After the treatment, the symptoms of the patients were significantly alleviated, and there was no recurrence during a 6-month follow-up.

In 2012, the Rheumatology and Immunology Department of Jiangsu University Affiliated Hospital intravenously infused umbilical cord mesenchymal stem cells for 21 patients with systemic lupus erythematosus, which significantly reduced the levels of urinary protein in these patients, decreased disease activity, and lowered the Systemic Lupus Erythematosus Disease Activity Index score.

The impact of mesenchymal stem cell transplantation on disease activity and urinary protein in patients with systemic lupus erythematosus (SLE)

In 2013, the Rheumatology and Immunology Department of the First Affiliated Hospital of Yangtze University and Jingzhou First People's Hospital administered umbilical cord mesenchymal stem cells via the anterior cubital vein to 18 patients with systemic lupus erythematosus. One month later, most patients showed significant improvement in clinical symptoms and signs such as fever, fatigue, and weakness compared to before transplantation.

06.anti-aging

The aging of the human body is related to insufficient or inactive stem cell quantity. As age increases, there is a downward trend in both the quantity and quality of stem cells in the body. This trend leads to the decline and aging of damaged cells and the organs and tissues composed of cells, resulting in suboptimal health and aging. Mesenchymal stem cells have the potential for multipotent differentiation, capable of differentiating into various types of stem cells needed in the body. By supplementing the insufficient stem cells in the body and repairing damaged organs and tissues, mesenchymal stem cells play a role in anti-aging.

With the increasing interest and application of umbilical cord mesenchymal stem cell research, it is believed that in the near future, they will be widely applied in clinical settings, thereby providing greater value to human health.