Therapeutic potential of human umbilical cord-derived mesenchymal stem cells in Crohn’s disease
In a recent study published in eBioMedicine, researchers investigated whether human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) could heal luminal ulcers in Crohn’s disease (CD) patients. CD is a developing global disease with a poor overall effectiveness rate, posing a considerable therapeutic challenge to health professionals. Current therapies have limitations, and recovery rates are far from expected. MSC-based therapy has demonstrated promise as a potential new treatment option for various disorders, including CD of the perianal fistulizing type. However, limited evidence is available on the efficacy of MSCs in treating or healing intestinal ulcers in CD. Human umbilical cord MSCs have acquired popularity due to their immunomodulatory capabilities, simplicity of collection, limitless source of stem cells, low immunological rejection, and lack of tumorigenic features. Despite their usefulness in immunological and inflammatory illnesses, there has been no research on using hUC-MSCs locally to heal intestinal ulcers in CD patients. The researchers induced experimental colitis to rat model and investigate the effectiveness of hUC-MSC therapy in CD. They calculated the disease activity index (DAI) by adding values for body weight loss, stool consistency, and stool blood. The colon macroscopic damage index (CMDI) assessed the level of colonic inflammation. They analyzed colon samples under a microscope to establish histopathological scores (HPS). From November 2020 to October 2023, the researchers ran a pilot, open-label clinical study with 17 refractory CD patients. Participants received a local submucosal injection of hUC-MSCs (60 × 106 cells/10 mL) by colonoscopy, followed by an intravenous drip of 1.0 × 106 hUC-MSCs/kg/100 mL the following day. The study included individuals aged 18–75 years with moderate-severe CD for ≥3 months, baseline CDAI scores of 220-450, and endoscopic ulcers. They did not respond to conventional or advanced treatment, including immunomodulators and biologics. The researchers followed the patients for 24 weeks, measuring laboratory and clinical markers on days 0, week 4, week 8, week 12, and week 24. They performed endoscopic assessments at the start of the trial and, after 12 weeks, obtained mucosal specimens from lesion margins for ribonucleic acid (RNA) sequencing. The researchers excluded individuals with a history of pregnancy, CD complications, comorbidities, prior surgery, uncontrolled infections, or cancer in the past five years. The team also produced two hUC-MSC in vitro co-cultures using mucosal tissues and the human monocyte cell line THP-1-induced M1 macrophages. Reverse transcription-polymerase chain reaction (RT-PCR) measured inflammatory and intestinal barrier function-related genes. In addition, the researchers performed gene ontology (GO) analysis and explored the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. They used enzyme-linked immunosorbent assays (ELISA) to assess the expression of tumor necrosis factor-stimulated gene-6 protein (TSG-6) in hUC-MSC culture supernatants after 48 hours of stimulation with lipopolysaccharide (LPS), interferon-gamma (IFNγ), and TNF-alpha (TNFα) for 48 hours. In preclinical studies, hUC-MSCs raised body weight while decreasing DAI, CMDI, and HPS scores in the TNBS-inflicted colitis murine model, with significant reductions in intestinal mucosal injury, edema, hyperemia, and ulcerations. Local and submucosal hUC-MSC injections resulted in intestinal ulcer regression in the study participants. Among the subjects, eight (47%) displayed endoscopic responses (a ≥50% improvement in SES-CD scores), and three (18%) demonstrated mucosal healing, with parallel improvements of laboratory and clinical markers without significant side effects. Human umbilical cord-derived MSCs increased transcripts associated with intestinal barrier integrity while decreasing those related to inflammatory intestinal mucosal pathways, including TNF-α, interleukin-17 (IL-17), and toll-like receptor (TLR) signaling. The treatment dramatically enhanced RNA levels of tight junction proteins [E-cadherin (CDH1), zonula occludens-1 (ZO1), and claudin-1 (CLDN1)] in the intestinal epithelium and intestinal pro-inflammatory genes (TNF-α, IL-1β, and IL-6). Furthermore, hUC-MSCs reduced THP1-induced M1 macrophage polarization and messenger RNA (mRNA) expressions of TNF-α, IL-1β, and IL-6. MSCs obtained from the human umbilical cord suppressed Janus kinase/signal transducers and activators of transcription (JAK/STAT) phosphorylation in intestinal mucosal cells from Crohn's disease patients. The study findings showed that submucosal injection of hUC-MSCs by colonoscopy, paired with an intravenous drip, reduced TNBS-inflicted colitis among rats. This technique may treat refractory CD with clinical effectiveness and tolerable risk. In individuals with moderately or highly active CD, hUC-MSC treatment resulted in clinical remission and the repair of intestinal ulcers. The expression of STAT1, M1 macrophage-associated specific markers, and pro-inflammatory factors in the intestinal mucosa dropped considerably following therapy. Further research is required to establish the efficacy of hUC-MSC treatment and investigate the underlying processes of the therapy.
Qinjuan Sun et al., (2024) hUC-MSCs therapy for Crohn’s disease: efficacy in TNBS-induced colitis in rats and a pilot clinical study, eBioMedicine, doi: https://doi.org/10.1016/j.ebiom.2024.105128. https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00163-4/fulltext
Development of autologous immunotherapies for cancer and leukemia from umbilical cord blood
Biohellenika R&D developed cancer immunotherapy protocols with autologous hematopoietic cord blood stem cells. Immunotherapies are personalized and targeted treatments, which are used in combination with other drugs to effectively treat cancer. Today 44 clinical trials are using umbilical cord blood to create immunotherapies for cancer, lymphomas and leukemia, while recently it has been announced that immunotherapies have reduced classic allogeneic hematopoietic transplants by 50%. Immunotherapies using autologous umbilical cord blood are based on the creation of dendritic cells, which are specialized for the specific malignancy antigens of the individual patient. Umbilical cord blood has an advantage over other sources, because it provides the largest number of highly active dendritic cells in a short time. Biohellenika's R&D developed a colon cancer immunotherapy protocol from umbilical cord blood. This treatment was tested on a colon cancer cell line and was highly effective. This protocol was published in the international journal, Differentiation 125 (2022) 54-61, and the company subsequently funded the development of a new immunotherapy protocol to treat leukemias. This protocol concerns the treatment of Acute Myeloid Leukemia, which usually appears after 60 years of life and the survival of patients with the usual treatments is short.
4/12/2023
Stem cell-based treatment controls blood sugar in people with Type 1 diabetes
November 27, 2023
University of British Columbia
:
An innovative stem cell-based treatment for Type 1 diabetes can meaningfully regulate blood glucose levels and reduce dependence on daily insulin injections, according to new clinical trial results. The therapy aims to replace the insulin-producing beta cells that people with Type 1 diabetes lack. Dubbed VC-02, the small medical implant contains millions of lab-grown pancreatic islet cells, including beta cells, that originate from a line of pluripotent stem cells.
An innovative stem cell-based treatment for Type 1 diabetes can meaningfully regulate blood glucose levels and reduce dependence on daily insulin injections, according to new clinical trial results from the University of British Columbia (UBC) and Vancouver Coastal Health (VCH).
"This is a significant step toward a functional cure for Type 1 diabetes," said Dr. David Thompson, principal investigator at the Vancouver trial site, clinical professor of endocrinology at UBC and director of the Vancouver General Hospital Diabetes Centre. "For the first time, a stem cell-based device can reduce the amount of insulin required for some trial participants with Type 1 diabetes. With further refinement of this approach, it's only a matter of time until we have a therapy that can eliminate the need for daily insulin injections entirely."
The findings, published today in Nature Biotechnology, arise from a multicenter clinical trial for an experimental cell therapy developed by U.S. biotechnology company ViaCyte (acquired by Vertex Pharmaceuticals) that is being clinically tested in Canada.
The therapy aims to replace the insulin-producing beta cells that people with Type 1 diabetes lack. Dubbed VC-02, the small medical implant contains millions of lab-grown pancreatic islet cells, including beta cells, that originate from a line of pluripotent stem cells.
The devices -- approximately the size of a Band-Aid and no thicker than a credit card -- are implanted just beneath a patient's skin where it is hoped they will provide a steady, long-term regulated supply of self-sustaining insulin.
"Each device is like a miniature insulin-producing factory," said co-author Dr. Timothy Kieffer, a professor within the departments of surgery and cellular and physiological sciences at UBC, and past chief scientific officer of ViaCyte. "The pancreatic islet cells, grown from stem cells, are packaged into the device to essentially recreate the blood sugar-regulating functions of a healthy pancreas. This may have tremendous benefits over transplant of scarcely available donor-derived cells, given that we can create a virtually limitless supply."
The clinical trial was conducted at Vancouver General Hospital, with additional sites in Belgium and the U.S. Ten participants, each of whom had no detectable insulin production at the start of the study, underwent surgery to receive up to 10 device implants each.
Six months later, three participants showed significant markers of insulin production and maintained those levels throughout the remainder of the year-long study. These participants spent more time in an optimal blood glucose range and reduced their intake of externally administered insulin.
One participant, in particular, showed remarkable improvement, with time spent in the target blood glucose range increasing from 55 to 85 per cent, and a 44-per-cent reduction in their daily insulin administration.
The results are the latest in a series of clinical trials funded by Canada's Stem Cell Network and conducted by the UBC-VCH team.
"The Stem Cell Network is delighted to support this clinical trial and we're pleased to see the promising results," said Cate Murray, president and CEO of the SCN. "Moving toward a functional cure for diabetes will require a coordinated and collaborative effort. It takes excellent science by top researchers in world-leading institutions, funders, like SCN, that de-risk research, and innovative biotech companies that can manufacture and scale the technology. SCN is proud to play its part and we look forward to what's next in game-changing diabetes research."
The trials aim to accelerate the development and clinical testing of novel stem-cell based therapies for the 300,000 Canadians living with Type 1 diabetes. Diabetes is estimated to cost the Canadian health-care system $29 billion annually.
Previously, in a 2021 study in Cell Stem Cell, the researchers were the first to show that the approach could produce insulin in the human body. The latest trial sought to significantly increase the amount of insulin produced by leveraging two-to-three times more devices per participant, alongside an updated device design with small perforations to allow for blood vessel ingrowth -- a feature aimed at improving survival of the lab-grown cells.
In another ongoing trial, the UBC-VCH team is investigating whether a version of the device containing cells that have been genetically engineered to evade the immune system, using CRISPR gene-editing technology, could eliminate the need for participants to take immunosuppressant drugs alongside the treatment.
"We envision a future where people with Type 1 diabetes are able to live their lives free from daily insulin injections and free from immune-suppressing drugs," said Dr. Thompson. "That future is now within reach, and Canada is leading the way in efforts to bring these novel treatments to patients."
Japan approves new stem cell-based Alzheimer's therapy
19:28 18 Jan 2024
In what could be a major breakthrough for Alzheimer's treatment, the Japanese Ministry of Health and Welfare has given the greenlight to a regenerative medicine technology based on administering fat-derived stem cells intravenously and into the spinal cord.
Developed by Korea's leading adult stem cell research institute, Biostar Stem Cell Research Institute, this new stem cell therapy involves administering 150-250 million stem cells intravenously and a further 50 million into the spinal cord cavity five times at intervals of two to four weeks.
“This is the first step in our project to overcome Alzheimer’s, which was launched with our commitment to conquer this disease,” Biostar Stem Cell Research Institute director Dr. Jeong-Chan Ra said.
“With the start of stem cell treatment, Biostar will support Alzheimer’s patients from all over the world – including Japan, Korea, China, and the US, starting in Japan – to restore their memory and ultimately their humanity.”
There are over 10 million new cases of dementia each year globally, with Alzheimer’s being the most common cause of the neurodegenerative disease.
Unlike most treatments for Alzheimer’s, which are limited to slowing the progression of disease, stem cell therapies are expected to offer a functional cure.
Testing on mice models revealed stem cell therapies offer a multi-pronged path of attack against Alzheimer's.
Mice who received the stem cell treatment improved in vital ways – cerebral vascular regeneration, and brain cell protection and regeneration were all observed following treatment, which also mediated the IL-10 cytokine.
IL-10 plays a central role in inflammation and neurological protection responses, particularly relevant given inflammation is considered to be one of the core contributors to cognitive decline.
An article by the BioSpectrum Bureau, a media platform for the healthcare and bioscience industry in the Asia Pacific region, stated: “No other compound or treatment has ever suggested so strongly the potential to prevent, as well as stop, this epidemic of incurable dementia sweeping across suffering patients and their families.”
Treatment has already begun at the Shinjuku Clinic in Tokyo, providing a sorely needed treatment pathway for those suffering from Alzheimer's.
Meta-Analysis of Cord Blood for Cerebral Palsy November 2023
Megan Finch-Edmondson, PhD, on behalf of the study team Megan Finch-Edmondson, PhD, lead author Introduction to cerebral palsy: Cerebral palsy is an umbrella term that describes a group of disorders affecting a person’s movement and posture. Cerebral palsy is a life-long condition that arises from injury to the brain during development, usually before, during or shortly after birth. Cerebral palsy is a highly variable condition. Symptoms may include difficulties in walking, balance and motor control, eating, swallowing, speech or coordination of eye movements. Cerebral palsy can vary in the way it affects an individual’s movement (type), the part of the body affected (topography) and by how severe the symptoms are (severity), which can be measured using the Gross Motor Function Classification System (GMFCS). In addition, people with cerebral palsy may also experience other impairments or co-occurring conditions such as epilepsy, behaviour disorders, or vision or hearing impairments. What treatments exist? Numerous interventions exist that help people with cerebral palsy to develop and maintain their functional skills as well as reduce the symptoms of cerebral palsy. These include various rehabilitative and medical interventions such as physical, occupational, and speech therapies, as well as botox injections, oral or intrathecal baclofen and even surgery to manage muscle stiffness and contractures. Currently there are no available treatments that directly target the underlying brain injury to improve function and quality of life. Why cell therapies? There is significant interest in investigating cell therapies such as umbilical cord blood as a treatment for cerebral palsy. This is because umbilical cord blood contains a variety of stem and progenitor cells that have been shown to be beneficial following a brain injury in laboratory research. These benefits include reducing inflammation and cell death, and promoting repair following a brain injury, mainly via release of cellular factors (“trophic mechanisms”). This may help to reduce the size or severity of an injury, and/or improve the connections within the brain. Cord blood for cerebral palsy: The earliest reported infusions of umbilical cord blood for cerebral palsy date back nearly 20 years. This was included in a paper published by Sun et al. in 2010 in which 140 children with cerebral palsy received autologous (their own) umbilical cord blood from March 2004 to December 20093. Since then, numerous studies have been published, with a 2021 review finding nearly 800 individuals with cerebral palsy had been treated with umbilical cord blood across all phases of clinical studies, including six medium/large randomised placebo-controlled trials. A 2016 systematic review concluded that cord blood treatment is safe and more effective than rehabilitation alone in improving gross motor function. Τhe study also suggested that umbilical cord blood treatment in children with cerebral palsy improved gross motor skills more than controls, and that higher cell dose and repeated treatments are likely beneficial, with data presented for the 6-month follow up timepoint.
https://parentsguidecordblood.org/en/news/meta-analysis-cord-blood-cerebral-palsy
Stem Cells Bank Biohellenika - Web design Hexabit - W3C - Pagespeed