Successful Stem Cell Treatment Of Autoimmune Diseases

Recent findings published in the Journal of Translational Medicine report the first ever treatment of autoimmune diseases with fat-derived stem cells. The article is entitled “Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells,” and contained contributions from researchers in five different countries: South Korea, United States, Japan, China, and Germany.

The senior author, Jeong Chan Ra, president of RNL Stem Cell Technology Institute, and his collaborators were successful in treating patients with autoimmune diseases who had experienced severe tissue damage as a result of their diseases and had limited treatment options.

Autoimmune diseases are caused by mis-regulation of the immune system that allows the body’s immune system to attack the very tissues and organs that house it. There are different kinds of autoimmune diseases which include systemic lupus erythematosis, rheumatoid arthritis, multiple sclerosis, autoimmune hearing loss, spastic myelitis, Bechet’s syndrome and so on.  Symptoms of autoimmune diseases are long-term, and these diseases often caused permanent damage.

In previous work, Ra’s team demonstrated the safety of intravenously infused adipose (fat)-derived stem cells in humans. Patients who received multiple stem cell infusions showed no adverse effects and no severe side effects. In this present study, the team showed that infusions of these stem cells were effective in treating diseases that ranged from autoimmune hearing loss, multiple sclerosis, polymyositis, atopic dermatitis, and rheumatoid arthritis, in this study.

In the case of autoimmune hearing loss, the patient was administered with her own stem cells. Her hearing returned to normal (scaled out to 15 decibels) even though she had previously not responded to steroid treatments.

A multiple sclerosis patient suffered severe side effects from high dose steroid treatments and had difficulty walking. However after infusions of her own stem cells, her condition improved tremendously, and she was able to move her legs using her own muscular strength.

Other autoimmune diseases treated in this paper were patients with multiple sclerosis, atopic dermatitis, and rheumatoid arthritis, all of whom were not able to be treated with existing medication. However, after multiple infusions of their own fat-derived stem cells, their illnesses became manageable.

Researchers are continuing to develop sophisticated stem cell technology using five grams of fat as a standard, which can be expanded to 1 billion stem cells. This technology became more efficient and convenient for patients because repetitive stem cell injections are possible from one time fat extraction. These studies also showed that the fat-derived stem cells were capable of homing to the site of damage where they were able to suppress the inflammation that was the cause of the pathology and symptoms of these diseases. These patients required less surgeries, transplants and fewer drugs.

Dr. Ra said: “The fact that we showed the way patients can be treated from their own stem cells is very rewarding to me. We are working towards becoming our country’s medical hub for treating autoimmune diseases.”

Engineering Blood Cells to Fight Melanoma

University of California, Los Angeles (UCLA) scientists have successfully completed a proof-of-principle experiment in mice that shows that blood cells can be re-engineered to become melanoma fighting immune cells.

Senior author on this study, Jerome Zack, who is also a scientist with UCLA’s Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, noted that genetic engineering techniques can remodel the blood cells of the mouse so that they form cancer-killing T-cells that seek out the tumor and destroy it. Zack stated: “We knew from previous studies that we could generate engineered T-cells, but would they work to fight cancer in a relevant model of human disease, such as melanoma. We found with this study that they do work in a human model to fight cancer, and it’s a pretty exciting finding.”

White blood cells come in several different varieties, but one group of white blood cells is the “lymphocytes,” which play an exceedingly central role in adaptive immunity. There are two main types of lymphocytes; B-lymphocytes, also known as B-cells and T lymphocytes or T-cells. T-cells receive their name from an organ that sits over the top part of the heart called the thymus. Once T-cells are born, they migrate to the thymus where they undergo a complex maturation process. Once they are released from the thymus into the peripheral circulation, they are ready to serve the immune system. T-cells differ from B-cells in that they possess a surface protein called the “T-cell receptor.” The T-cell receptor recognized foreign substances or “antigens” that are bound to the surfaces of cells. When the T-cell binds to this antigen, it becomes activated and begins to divide and initiates the formation of an immune response against this antigen.

In this experiment, Zack and his co-workers used a T-cell receptor that they had isolated from a cancer patient. This particular T-cell receptor recognized an antigen that is specific to melanomas. The UCLA group then used genetic engineering techniques to place the T-cell receptor gene into the blood-making stem cells in the bone marrow of laboratory mice. After re-introducing these engineered blood-making stem cells into the experimental mice. Next, Zack and his colleagues transplanted a small piece of human thymus into the experimental mice. This gave the mice a place to allow the newly made T-cells to mature.

After approximately six weeks, engineered blood stem cells had formed a large population of mature, melanoma-specific T-cells that were able to target the particular cancer cells. To demonstrate this, the experimental mice were then implanted with two types of melanoma, one that expressed the antigen complex recognized by the T-cell receptor introduced into the bone marrow stem cells, and another tumor that did not. The engineered cells specifically went after the melanoma that expressed the particular antigen, but they left the other tumor alone. Of the nine nude mice used in this study, four animals showed complete elimination of the antigen-expressing melanomas, and the other five showed a marked decrease in the size of the tumors. The immune response against the tumors was determined not only by measuring physical tumor size, but by monitoring the cancer’s metabolic activity using Positron Emission Tomography (PET), which measures how much energy the cancer is “eating” to drive its growth.

Zach noted: “We were very happy to see that four tumors were completely gone and the rest had regressed, both by measuring their size and actually seeing their metabolic activity through PET.” Zack said.

This approach has the advantage of engineering only a few cells that can produce a veritable army of cancer-fighting T-cells. Furthermore, these cells can exist in the circulating blood in low numbers, but if they detect the melanoma antigen, they can replicate and expand their numbers quickly and home to the tumor where they will fight it. Other advantages of this strategy are that the function of the engineered T-cells is not long-lasting in most cases. More engineered T-cells ultimately are needed to sustain a response, but some of these cells will probably become “memory cells.” Memory cells are inactive cells that remember the infection they recently fought, but can be reactivated if they encounter the antigen once again. This suggests that “fresh” cancer-killing cells could be easily generated when needed, perhaps protecting against cancer recurrence later.

The team would like to test this approach in clinical trials. One possible approach would be to engineer both the circulating T-cells and the blood stem cells that give rise to T-cells. The peripheral T-cells would serve as the front line cancer fighters, while the blood stem cells are creating a second wave of warriors to take up the battle as the front line T-cells are losing function. Zack also said that he hopes that this technique could adapted for protocols the battle other cancers like breast and prostate cancers.