A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial

Sarveazad, Arash; Newstead, Graham L.; Mirzaei, Ramazan; Joghataei, Mohammad Taghi; Bakhtiari, Mitra; Babahajian, Asrin; Mahjoubi, Bahar

doi:10.1186/s13287-017-0489-2

Cited by 59 publications

(77 citation statements)

References 42 publications

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“…However, the number of patients was limited and heterogeneous and the follow-up time short. Despite these limitations, they discovered an increase in total muscle area in an endorectal sonography assessment in the hASC treatment group compared with the saline control group [20]. In our study, the anal pressures were comparable with the other animal studies although there are slight variations-possibly due to different techniques (balloon vs. double-triple-lumencatheter, electrical stimulation vs. spontaneous contraction) and different size of the anal canal in different species [13,16,19].…”

Section: Discussionsupporting

confidence: 57%

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Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

Kuismanen

Juntunen

Narra

et al. 2018

Stem Cells Translational Medicine

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Anal incontinence is a devastating condition that significantly reduces the quality of life. Our aim was to evaluate the effect of human adipose stem cell (hASC) injections in a rat model for anal sphincter injury, which is the main cause of anal incontinence in humans. Furthermore, we tested if the efficacy of hASCs could be improved by combining them with polyacrylamide hydrogel carrier, Bulkamid. Human ASCs derived from a female donor were culture expanded in DMEM/F12 supplemented with human platelet lysate. Female virgin Sprague‐Dawley rats were randomized into four groups (n = 14–15/group): hASCs in saline or Bulkamid (3 × 105/60 μl) and saline or Bulkamid without cells. Anorectal manometry (ARM) was performed before anal sphincter injury, at two (n = 58) and at four weeks after (n = 33). Additionally, the anal sphincter tissue was examined by micro‐computed tomography (μCT) and the histological parameters were compared between the groups. The median resting and peak pressure during spontaneous contraction measured by ARM were significantly higher in hASC treatment groups compared with the control groups without hASCs. There was no statistical difference in functional results between the hASC‐carrier groups (saline vs. Bulkamid). No difference was detected in the sphincter muscle continuation between the groups in the histology and μCT analysis. More inflammation was discovered in the group receiving saline with hASC. The hASC injection therapy with both saline and Bulkamid is a promising nonsurgical treatment for acute anal sphincter injury. Traditional histology combined with the 3D μCT image data lends greater confidence in assessing muscle healing and continuity. Stem Cells Translational Medicine 2018;7:295–304

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Section: Discussionsupporting

confidence: 57%

“…Mesenchymal stem cells (MSC) derived from bone marrow have been used in a few studies and the results are promising [17][18][19]. Additionally, a small clinical trial with human adipose stem cells (hASCs) has recently been published [20].…”

Section: Introductionmentioning

confidence: 99%

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

Kuismanen

Juntunen

Narra

et al. 2018

Stem Cells Translational Medicine

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“…179 The group of Sarveazad and colleagues reported no significant functional improvement but observed structural replacement of scar tissue with muscle fibres in faecal incontinence patients. 180 The lack 181 Interestingly, there was no difference in functional outcome between the myoblast and placebo groups at the 6 month followup, but a significant difference was observed after 12 months. This may either be indicative of time taken for engraftment and maturation of myofibers into contractile units or suggest that the bulking effect due to injection also aids in ameliorating continence in the placebo group for a short time period (6 months).…”

Section: Translating Pre-clinical Promise Into Clinically Successful mentioning

confidence: 96%

“…reported the safety and tolerability of allogeneic adipose tissue‐derived MSCs with doses of 30–90 × 10 6 cells after injection into the anal sphincter muscles but did not report whether any functional or structural benefits were observed . The group of Sarveazad and colleagues reported no significant functional improvement but observed structural replacement of scar tissue with muscle fibres in faecal incontinence patients . The lack of any functional improvement may be attributed to the relatively low dosage (6 × 10 6 cells) administered.…”

Section: Translating Pre‐clinical Promise Into Clinically Successful mentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

110

128

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Diseases that jeopardize the musculoskeletal system and cause chronic impairment are prevalent throughout the Western world. In Germany alone, ~1.8 million patients suffer from these diseases annually, and medical expenses have been reported to reach 34.2bn Euros. Although musculoskeletal disorders are seldom fatal, they compromise quality of life and diminish functional capacity. For example, musculoskeletal disorders incur an annual loss of over 0.8 million workforce years to the German economy. Among these diseases, traumatic skeletal muscle injuries are especially problematic because they can occur owing to a variety of causes and are very challenging to treat. In contrast to chronic muscle diseases such as dystrophy, sarcopenia, or cachexia, traumatic muscle injuries inflict damage to localized muscle groups. Although minor muscle trauma heals without severe consequences, no reliable clinical strategy exists to prevent excessive fibrosis or fatty degeneration, both of which occur after severe traumatic injury and contribute to muscle degeneration and dysfunction. Of the many proposed strategies, cell‐based approaches have shown the most promising results in numerous pre‐clinical studies and have demonstrated success in the handful of clinical trials performed so far. A number of myogenic and non‐myogenic cell types benefit muscle healing, either by directly participating in new tissue formation or by stimulating the endogenous processes of muscle repair. These cell types operate via distinct modes of action, and they demonstrate varying levels of feasibility for muscle regeneration depending, to an extent, on the muscle injury model used. While in some models the injury naturally resolves over time, other models have been developed to recapitulate the peculiarities of real‐life injuries and therefore mimic the structural and functional impairment observed in humans. Existing limitations of cell therapy approaches include issues related to autologous harvesting, expansion and sorting protocols, optimal dosage, and viability after transplantation. Several clinical trials have been performed to treat skeletal muscle injuries using myogenic progenitor cells or multipotent stromal cells, with promising outcomes. Recent improvements in our understanding of cell behaviour and the mechanistic basis for their modes of action have led to a new paradigm in cell therapies where physical, chemical, and signalling cues presented through biomaterials can instruct cells and enhance their regenerative capacity. Altogether, these studies and experiences provide a positive outlook on future opportunities towards innovative cell‐based solutions for treating traumatic muscle injuries—a so far unmet clinical need.

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“…Allogeneic cell transplantation for FI may be feasible in the future with modifications to established immunosuppressive protocols. In addition, adipose‐tissue‐derived mesenchymal stem cells, which have pluripotent abilities when inflammatory responses are suppressed, may have potential benefits for FI .…”

Section: Discussionmentioning

confidence: 99%

Isolation of internal and external sphincter progenitor cells from the human anal sphincter with or without radiotherapy

et al. 2018

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A new method for treating fecal incontinence by implanting stem cells derived from human adipose tissue: preliminary findings of a randomized double-blind clinical trial

Cited by 59 publications

References 42 publications

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

Functional Outcome of Human Adipose Stem Cell Injections in Rat Anal Sphincter Acute Injury Model

Cell therapy to improve regeneration of skeletal muscle injuries

Isolation of internal and external sphincter progenitor cells from the human anal sphincter with or without radiotherapy

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