Pregnancy and Delivery Unaffected in Women Patients With Crohn’s Disease Who Were Treated With Fat-Based Stem Cells


Fat is a readily accessible source of mesenchymal stem cells (MSCs). When fat is extracted by liposuction, the result is a so-called stromal vascular fraction (SVF) that contains a mishmash of mast cells (important in allergies), blood vessel-making cells, blood vessel-associated cells, fibroblasts, and MSCs. These adipose-derived stem cells (ASCs) as they are called, can be relatively easily prepared once the SVF is digested by enzymes, and centrifuges. The living adult MSCs are then rather easily identified because they adhere to plastic tissue culture plates.

Fat-based MSCs have been used in clinical studies to help heal patients with Crohn’s disease who have “fistulas.”  For a picture of a fistula, see here.  Crohn’s disease (CD) is one of a group of gastrointestinal diseases known as IBDs or inflammatory bowel diseases. CD features inflammation of any part of the GI tract, and this inflammation can affect multiple layers of the GI tract. Fistulas form when a hole is eroded through the GI tract and into another organ system. For example, in women, the rectum and erode and form an opening in the vagina. Alternatively, an opening can appear in some place other than the anus. Because of the repeated irritation and extensive inflammation of these lesions, they tend to not heal.

Beginning in 2003, Damián García-Olmo and his team at the Jiménez Diaz Foundation University Hospital in Madrid, Spain have tested the efficacy of fat-based stem cells in treating patients with CD-based fistulas.  The results have been encouraging and highly positive, since ASCs promote healing of the fistulas and decrease recovery time (see de la Portilla F, et al. (2013) Int J Colorectal Dis 28:313–323; García-Olmo D, et al. (2003) Int J Colorectal Dis 18:451–454; García-Olmo D, et al. (2005) Dis Colon Rectum 48:1416–1423; Garcia-Olmo D, et al. (2009) Dis Colon Rectum 52:79–86).

Recently, Garcia-Olmo and his colleagues examined data from several their patients who went on to become pregnant after their treatment with fat-based stem cells and even given birth. This study, which was published in the June 2015 edition of Stem Cells Translational Medicine, examined six patients from these previous clinical trials who were successfully treated with fat-based stem cells, had satisfactory resolution and healing of their lesions, and then went on to become pregnant and give birth.

Of the five women examined in this study, one was treated for rectovaginal and perinatal fistulas, two for rectovaginal fistulas only, and two others for perianal fistulas only. All women received 2 doses of 20 million and 40 million stem cells at three-four-month intervals. One patient, however, received 2 doses of 6.6 million and 20 million stem cells nine months apart.

The fertility of these women and their pregnancies were unaffected by their previous cell therapies. There were no signs of treatment-related malformations in the babies they delivered, and their bodies did not show any identifiable signs of structural abnormalities as a result of the stem cell treatments. It must be said, that all four women who delivered healthy babies (one of them even had twins) elected for Caesarian sections. The fifth woman, unfortunately, miscarried twice, both times during the first trimester.

However, even though this represents a small data set, this study does strongly suggest that injection of a patient’s own fat-based stem cells does not negatively affect a woman’s ability to conceive, the course of her pregnancy, or the health of her baby.

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Stem Cell-Based Exosomes Heal Hearts After a Heart Attack


A new paper in the journal Circulation Research by a research team from the Temple University School of Medicine (TUSM) has examined the use of tiny stem cell-based vesicles to help limit the damage caused by a heart attack. Even those these experiments were performed with laboratory mice, the result are very promising.

A heart attack tends to badly damage it, and since the heart has little innate ability to repair itself, it has to compensate by growing large and flabby, which can lead to congestive heart failure, Congestive heart failure is currently responsible for one in nine deaths in the United States.

The research team of Raj Kishore at the Temple University School of Medicine turned to exosomes to heal the heart. Exosomes are tiny sacks secreted by cells that act as messengers that pass messengers between cells in various parts of the body. While these extracellular vesicles are secreted by nearly all types of cell, exosomes from stem cells might be a useful tool in mitigating damage caused by heart attacks.

Exosomes
Exosomes

“If your goal is to protect the heart, this is a pretty important finding,” Dr. Kishore said. “You can robustly increase the heart’s ability to repair itself without using the stem cells themselves. Our work shows a unique way to regenerate the heart using secreted vesicles from embryonic stem cells.”  Kishore’s group is also beginning to determine those members of this “work crew” within the vesicles may be responsible for the damage repair.

Previous studies have shown that injecting damaged hearts with stem cells increases heart function after a heart attack. However, the injected cells tend to not survive very long when placed in the damaged heart, and most of their benefits are due to molecules that the administered stem cells secrete. Pluripotent stem cells (embryonic stem cells, for example) run the risk of creating a tumor made up of a mass of cells of different tissue types, known as a teratoma. Therefore, Khan’s tram approached the problem from a slightly different angle by injecting only the exosomes made by stem cells. It was known that this would avoid the teratoma problem, and could have positive effects on damaged heart tissue.

Exosome poster

The study examined mice that had suffered heart attacks. These animals were split into two groups; one group received exosomes from mouse embryonic stem cells, and the other group were injected with fibroblast exosomes.

The results were extremely promising. The mice that had received stem cell-derived exosomes exhibited improved heart function, less scar tissue, lower levels of programmed cell death and better capillary development around the damaged area. There was also a higher presence of cardiac progenitor cells – the heart’s own stem cells – in the stem cell exosome-injected mice. Overall, the heartbeat of the mice was stronger than those in the control group, with less unhealthy enlargement of the organ.

Khan and others examined an abundant gene-regulating molecule (microRNA) from the stem cell-derived exosomes, known as miR-294. They introduced this microRNA into cultured cardiac stem cells. This microRNA recapitulated many of the positive effects of the stem cell exosomes that had been observed in the animal study.

Khan and his coworker plan to continue their research by studying the effects of individual microRNAs on damaged heart tissue.

“Our work shows that the best way to regenerate the heart is to augment the self-repair capabilities and increase the heart’s own capacity to heal,” says researcher Dr Mohsin Khan. “This way, we’re avoiding risks associated with teratoma formation and other potential complications of using full stem cells. It’s an exciting development in the field of heart disease.”