Stem Cells Show Promise in the Treatment of Failing Hearts
New research presented by a team from Rigshospitalet University Hospital Copenhagen (Copenhagen, Denmark) at the American College of Cardiology’s 63rd Annual Scientific Session suggests that heart failure patients may benefit from a new treatment in which stem cells derived from bone marrow are injected into the heart.
Heart failure is a leading cause of mortality and morbidity. Treatments are available but many patients are still dramatically debilitated by the disease. This study is the largest placebo-controlled, double-blind randomized trial to use mesenchymal stromal cells injected directly into the heart muscle to treat patients with chronic ischemic heart failure. Previous studies have demonstrated that mesenchymal stromal cells can stimulate repair in various tissues, including heart muscle.
A total of 59 patients with chronic ischemic heart disease and heart failure were included in the study. A small amount of bone marrow was extracted from each patient and the mesenchymal stromal cells were then isolated and induced to self-replicate. Patients were then given an injection containing either a saline placebo or their own cultured mesenchymal stromal cells directly into the heart muscle via a catheter inserted in the groin; a procedure requiring only local anesthesia.
After 6 months, treated patients showed an 8.2-ml decrease in end systolic volume, the study’s primary end point and a key measure of the heart’s pumping ability. An increase in end systolic volume of 6 ml was observed in patients in the placebo group.
These results support previous findings from smaller studies that demonstrated reduced scar tissue in the heart in patients treated with stem cells. Researchers will now continue to monitor these patients in order to evaluate the long-term outcomes. A larger, Phase III clinical trial is now required in order to progress towards the acceptance of this treatment for widespread use in patients with ischemic heart failure.
– Written by Caroline Telfer
Source: American College of Cardiology press release: www.cardiosource.org/News-Media/Media-Center/News-Releases/2014/03/Mathiasen-Stem-Cell.aspx?w_nav=Search&WT.oss=failing%20hearts&WT.oss_r=870&
Nose Reconstruction Using Tissue-Engineered Cartilage
Five patients with defects after excision of nonmelanoma skin cancer on the alar lobule have had nose reconstruction using engineered autologous cartilage grafts. The study, which took place at the University Hospital Basel (Switzerland), has been reported in a recent issue of Lancet.
All five patients, aged 76–88 years, had a two-layer defect (≥50% size of alar subunit) on the alar lobule after a tumor resection of nonmelanoma skin cancer. The standard procedure involves grafts taken from the nasal septum, the ear or the ribs to functionally reconstruct the nose. However, this procedure is very invasive, painful and can lead to complications.
The investigators extracted a small biopsy from each patient, isolated the cartilage cells and cultured them. The expanded cells were seeded onto a collagen membrane and cultured for 2 additional weeks, generating cartilage 40-times the size of the original biopsy. The engineered grafts were shaped to match the patients and the implanted.
Ivan Martin, Professor for Tissue Engineering at the Department of Biomedicine at the University Hospital of Basel and author of Regenerative Medicine Applications in Organ Transplantation in this issue of Regenerative Medicine, said, “The engineered cartilage had clinical results comparable to the current standard surgery. This new technique could help the body to accept the new tissue better and to improve the stability and functionality of the nostril.”
Martin continued, “Our success is based on the long-standing, effective integration in Basel between our experimental group at the Department of Biomedicine and the surgical disciplines at the University Hospital. The method opens the way to using engineered cartilage for more challenging reconstructions in facial surgery such as the complete nose, eyelid or ear.”
Martin concluded, “We need rigorous assessment of efficacy on larger cohorts of patients and the development of business models and manufacturing paradigms that will guarantee cost–effectiveness.”
The same engineered grafts are currently being tested in a parallel study for articular cartilage repair in the knee.
– Written by Theo Bond
Source: Fulco I, Miot S, Haug MD et al. Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial. The Lancet doi:10.1016/S0140-6736(14)60544-4 (2014) (Epub ahead of print); University of Basel press release: www.unibas.ch/index.cfm?uuid?4AF13BFCE4DD3FB84DA97A5566E64C81&type?search&show_long?1&o_lang_id?2
Vagina Reconstruction Using Tissue-Engineered Organs
A paper published in a recent issue of The Lancet has shown the results of an 8-year follow of patients who had vaginal reconstruction using autologous tissue engineering and biodegradable scaffolds. The study was carried out as a joint effort between the Wake Forest Institute for Regenerative Medicine (NC, USA) and Hospital Infantil de México Federico Gómez (Mexico).
Vaginal reconstruction can be a required for a number of disorders such as congenital abnormalities, injury or cancer; however, the use of nonvirginal tissue can be associated with complications. This pilot study developed autologous tissue-engineered vaginal organs for four patients with vaginal aplasia caused by Mayer-Rokitansky-Küster-Hauser syndrome.
The four patients had a vulvar biopsy to attain the autologous tissue, which was then cultured, expanded and seeded onto biodegradable scaffolds. After maturation in an incubator, the organs were implanted and the patients were followed up for 8 years.
“Really for the first time we’ve created a whole organ that was never there to start with, it was a challenge,” said Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest. Atala added that this procedure was a “very important thing” for these women and the difference that the procedure had “was very rewarding to see.”
The researchers noted no long-term postoperative surgical complications, with yearly biopsies and immunohistochemistry analysis confirming the presence of phenotypically normal smooth muscle and epithelia. In addition, a validated self-administered Female Sexual Function Index questionnaire showed variables in the normal range in a number of areas such as arousal, lubrication, orgasm and painless intercourse.
Martin Birchall, Professor at University College of London (UK) who worked on laboratory-grown windpipes, commented, “These authors have not only successfully treated several patients with a difficult clinical problem, but addressed some of the most important questions facing translation of tissue engineering technologies.” Birchall concluded, “The steps between first-in-human experiences such as those reported here and their use in routine clinical care remain many, including larger trials with long-term follow-up, the development of clinical grade processing, scale-out, and commercialization.”
– Written by Theo Bond
Sources: Raya-Rivera AM, Esquiliano D, Fierro-Pastrana R et al. Tissue-engineered autologous vaginal organs in patients: a pilot cohort study. Lancet doi:10.1016/S0140-6736(14)60542-0 (2014) (Epub ahead of print); BBC News story: www.bbc.co.uk/news/health-26885335