Immunomodulatory placental‐expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty

Winkler, Tobias; Perka, Carsten; Roth, Philipp von; Agres, Alison N.; Plage, Henning; Preininger, Bernd; Pumberger, Matthias; Geißler, Sven; Hagai, Esther Lukasiewicz; Ofir, Racheli; Pinzur, Lena; Eyal, Eli; Stoltenburg‐Didinger, Gisela; Meisel, Christian; Consentius, Christine; Streitz, Mathias; Reinke, Petra; Duda, Georg N.; Volk, Hans‐Dieter

doi:10.1002/jcsm.12316

Cited by 51 publications

(68 citation statements)

References 40 publications

(37 reference statements)

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“…A statistically significant reduction of stress leaks in all dose groups was observed compared with baseline . In the first clinical study of its kind, skeletal muscle injury associated with hip arthroplasty surgeries was treated by local administration of allogeneic placenta‐derived MSCs in a small cohort of patients . Cells were delivered intraoperatively after thawing.…”

Section: Translating Pre‐clinical Promise Into Clinically Successfulmentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

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106

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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Section: Translating Pre‐clinical Promise Into Clinically Successfulmentioning

confidence: 99%

Cell therapy to improve regeneration of skeletal muscle injuries

Qazi

Duda

Ort

et al. 2019

J cachexia sarcopenia muscle

Self Cite

106

128

View full text Add to dashboard Cite

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“…In a randomized phase I/IIa study (NCT01525667) conducted by Pluristem Therapeutics (Haifa, Israel), 20 patients undergoing hip arthroplasty received an injection of either 300 or 150 million placental‐expanded, mesenchymal stromal cells or placebo into the surgically affected gluteus medius muscles. In this study, both treatment arms demonstrated greater improvement in gluteus medius muscle strength at 6, 12, and 26 weeks after surgery . Pluristem is currently planning a study to assess the efficacy of similar treatment in individuals after hip fracture (NCT03451916).…”

Section: Nonpharmacological Regenerative Medicine Approachesmentioning

confidence: 80%

“…In this study, both treatment arms demonstrated greater improvement in gluteus medius muscle strength at 6, 12, and 26 weeks after surgery. 78 Pluristem is currently planning a study to assess the efficacy of similar treatment in individuals after hip fracture (NCT03451916).…”

Section: Nonpharmacological Regenerative Medicine Approaches Stem Cellsmentioning

confidence: 99%

Emerging Interventions for Elderly Patients—The Promise of Regenerative Medicine

Miller

Roubenoff

2018

Clin Pharma and Therapeutics

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The impressive increase in lifespan that occurred in the 20th century has driven a boom in age‐associated degeneration resulting from senescence. Geriatric syndromes, such as sarcopenia and frailty, do not fall neatly into classical medical definitions of disease because they result from subtle declines in physiological function that occur over many years instead of specific organ‐related pathology. These conditions have become more clinically prominent with the aging population and are the focus of research in regenerative medicine. Two major approaches are being pursued: the first targets specific organs that are adversely affected by senescence, and the second targets senescence pathways themselves, with the goal of favorably altering the affected physiology. This review will highlight a few examples of recent applications of both of these approaches to illustrate the potential of the application of a regenerative medicine approach to improve the quality of life and independence in older adults.

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“…(Local) reduction of conventional T‐cell levels and concurrent enrichment of regulatory T cells is a promising therapeutic strategy to further improve muscle repair. In this regard, Winkler et al . (Charité University Berlin, Berlin, Germany) presented data from the HIPGEN study, which is now in Phase III.…”

Section: Clinical Trials and New Treatment Targetsmentioning

confidence: 99%

“…(Local) reduction of conventional T-cell levels and concurrent enrichment of regulatory T cells is a promising therapeutic strategy to further improve muscle repair. In this regard, Winkler et al 48 (Charité University Berlin, Berlin, Germany) presented data from the HIPGEN study, which is now in Phase III. This randomized, double-blind, placebo-controlled study addresses surgical trauma-related muscle injuries using local intraoperative application of allogeneic placentaderived, mesenchymal-like adherent cells, using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type.…”

Section: Clinical Trials and New Treatment Targetsmentioning

confidence: 99%

Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 12th Cachexia Conference

Ebner

Anker

Haehling

2020

J cachexia sarcopenia muscle

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This article highlights preclinical and clinical studies in the field of wasting disorders that were presented at the 12th Cachexia Conference held in Berlin, Germany, in December 2019. Herein, we summarize the biological and clinical significance of different strategies including antibodies that target Fn14, Spsb 1, SAA1 treatment, ZIP14, a MuRF1 inhibitor, and new diagnostic tools like T‐cell communication targets and cut‐offs for the detection of skeletal muscle wasting. Of particular interest were the transplantation of mesenchymal stromal cells and muscle stem cell communication. Importantly, one presentation discussed the effect of metal ion transporter ZIP14 loss that reduces cancer‐induced cachexia. The potential of anti‐ZIP14 antibodies and zinc chelation as anti‐cachexia therapy may require testing in patients with cancer cachexia. Large clinical studies were presented such as RePOWER (observational study of patients with primary mitochondrial myopathy), MMPOWER (treatment with elamipretide in patients with primary mitochondrial myopathy), and ACT‐ONE as well as new mouse models like the KPP mouse. Promising treatments include rapamycin analogue treatment, anamorelin, elanapril, glucocorticoids, SAA1, antibodies that target Fn14, and a MuRF1 inhibitor. Clinical studies investigated novel approaches, including the role of exercise. It remains a fact, however, that effective treatments for cachexia and wasting disorders are urgently needed in order to improve patients' quality of life and their survival.

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Immunomodulatory placental‐expanded, mesenchymal stromal cells improve muscle function following hip arthroplasty

Cited by 51 publications

References 40 publications

Cell therapy to improve regeneration of skeletal muscle injuries

Cell therapy to improve regeneration of skeletal muscle injuries

Emerging Interventions for Elderly Patients—The Promise of Regenerative Medicine

Recent developments in the field of cachexia, sarcopenia, and muscle wasting: highlights from the 12th Cachexia Conference

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