Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

Ciapetti, G.; Granchi, Donatella; Fotia, Caterina; Savarino, L.; Piccolo, Nicolandrea Del; Donati, Davide María; Baldini, Nicola

doi:10.1016/j.jcyt.2016.06.005

Cited by 40 publications

(28 citation statements)

References 62 publications

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“…This case of FHAVN improved significantly after a prolonged course of laser acupuncture. However, in some orthopedic sources, noninvasive treatments like inhalation of hyperbaric oxygen, mesenchymal stromal cell therapy, gene therapy carrying growth factor, and vascular endothelial growth factor 20,21 have been mentioned, but to the best of our knowledge, it is the first report using low-level laser therapy as a treatment for AVN of the femoral head. It seems that this study has been able to show the effect of LLLT on AVN treatment, for the first time.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Radiographic Alterations in Bilateral Avascular Necrosis of the Femoral Head Following Laser Acupuncture: A Case Report

et al. 2018

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Avascular necrosis (AVN) of the femoral head is an increasingly common cause of musculoskeletal disability with unknown etiology. Traumatic and non-traumatic factors can be effective in its occurrence. About 50% of cases are bilateral. The underlying treatment is prosthetic replacement surgical procedure. We report a case of bilateral AVN of femoral heads who was a candidate for prosthetic replacement surgery but improved significantly, using laser acupuncture. The patient was a 55-year-old woman with a diagnosis of bilateral osteonecrosis of the femoral head for five years. As the patient declined the surgical option, laser acupuncture was started for pain control. Regarding the signs of bilateral femoral head recovery (according to the MRI scan criteria), a total of 3 courses of laser acupuncture (each course was 20 sessions) with 2 months intervals was performed. Ten acupuncture points: Li4, Li11, St36, SP6, LIV3, GB4, GB5, GB6, GB13, GB14, GB20, GB30, GB31, GB34, were irradiated bilaterally using red 650 nm laser, 100 mW, 1505 Hz frequency, duty cycle 50 3 J/point and near infrared 810 nm laser, 100 mW, 1705 Hz frequency, duty cycle 50 3 J/point, for 2 minutes. The patient received 3 laser therapy courses. During the first-course, laser therapy was done every other day to reduce pain. For the second and third courses, according to pain decrease, therapy was done every week. The results of the MRI scans and x-ray studies show progressive regeneration of the right femoral head from VI to B II and of the left from V to C II (based on the standard table of Pennsylvania). It seems that this procedure may be mentioned in future research projects, especially in cases with high risks of surgery.

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Section: Discussionmentioning

confidence: 99%

Clinical and Radiographic Alterations in Bilateral Avascular Necrosis of the Femoral Head Following Laser Acupuncture: A Case Report

et al. 2018

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“…Since the underlying cause of osteonecrosis is speculated to be ischemia, and since MSC enhance the blood flow to ischemic tissues [ 28 – 31 ], it is reasonable to expect them to exert a considerable prophylactic effect against the development of osteonecrosis. In contrast, direct implantation of MSC at injured sites would be highly invasive and require specialized technique.…”

Section: Discussionmentioning

confidence: 99%

Prevention of glucocorticoid-associated osteonecrosis by intravenous administration of mesenchymal stem cells in a rabbit model

Ueda

Shimasaki

Ichiseki

et al. 2017

BMC Musculoskelet Disord

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BackgroundGlucocorticoid-associated osteonecrosis is an intractable condition, making the establishment of preventative strategies of particular importance. Recently various studies using mesenchymal stem cells (MSC) have been conducted. Using a rabbit glucocorticoid-associated osteonecrosis model we administered green fluorescent protein (GFP)-labeled MSC intravenously to investigate their effect on osteonecrosis.MethodsA rabbit osteonecrosis model in which methylprednisolone (MP) 20 mg/kg was injected into the gluteus of a Japanese white rabbit was used. Simultaneously with MP, MSC labeled with GFP (GFP-labeled MSC) were injected intravenously. Fourteen days later the animals were killed (MSC(+)/MP(+)/14d), femurs were extracted, and the prevalence of osteonecrosis was determined histopathologically. Also, animals were killed 3 days after simultaneous administration of GFP-labeled MSC and MP (MSC(+)/MP(+)/3d), and western blotting (WB) for GFP was performed of the femur, liver, kidney, lung, blood vessel, and vertebra, in addition to immunohistochemical study of femur. As a control for the histopathological study, animals were killed 14 days after MP administration and intravenous vehicle injection (MSC(−)/MP(+)/14d). For WB, animals were killed 3 days after intravenous GFP-labeled MSC administration and vehicle injection into the gluteus (MSC(+)/MP(−)/3d).ResultsIn MSC(−)/MP(+)/14d osteonecrosis was found in 7 of 10 rabbits (70%), while in MSC(+)/MP(+)/14d, partial bone marrow necrosis was found in only 1 rabbit (12.5%); osteonecrosis was not found in 7 of 8 rabbits (p < 0.05). WB showed expression of GFP in the femur, not in the liver, kidney, lung, blood vessel, or vertebra, of MSC(+)/MP(+)/3d; expression of GFP-labeled MSC was absent in the femur of MSC(+)/MP(−)/3d. In the immunohistochemical study of MSC(+)/MP(+)/3d, homing of GFP-labeled MSC was noted perivascularly in the femur, but not in MSC(+)/MP(−)/3d.ConclusionsWith transvenous MSC administration a significant prophylactic effect against glucocorticoid-associated osteonecrosis was found. Direct administration of MSC to the site of tissue injury requires highly invasive surgery. In contrast, as shown here the simple and hardly invasive intravenous administration of MSC may succeed in preventing osteonecrosis.Electronic supplementary materialThe online version of this article (10.1186/s12891-017-1837-1) contains supplementary material, which is available to authorized users.

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“…The results of studies on osteogenic differentiation of human MSCs were also characterized by large individual variability. This has manifested itself, among others, through a large diversity in the deposition ability of the mineralized matrix, intra-group fluctuations in the proliferative index and the ability to form colonies for cells from different patients under both, the normoxia and hypoxia conditions (Ciapetti et al, 2016). Interestingly, using an animal system in vivo, it was observed that a decrease in blood flow within the dental pulp results in increased mineralization and differentiation of DPSCs in the rat odontoblast layer (Ito et al, 2015).…”

Section: The Effect Of Oxygen Concentration On Stem Cellsmentioning

confidence: 99%

“…In this context, in order to elucidate a more complete and accurate mechanism of the impact of hypoxia and other factors on osteogenic differentiation of MSCs, with particular emphasis on future applications of these results in regenerative medicine, it is important to optimize the methods used for the cell isolation and ex vivo propagation. Discrepancies in the methodology often resulted in contradictory data obtained by different groups studying MSC potential (Kumar & Vaidya, 2016;Hsu et al, 2013;Hung et al, 2012;Ciapetti et al, 2016;Ito et al, 2015;Iida et al, 2010;Ahmed et al, 2016). Thus, further optimization of the protocols for the effective harvesting and expansion of MSCs with high differentiation potential as well as strategies for examining their biological properties and proregenerative mechanisms, are still required to fully understand the application potential of these cells .…”

Section: The Effect Of Oxygen Concentration On Stem Cellsmentioning

confidence: 99%

Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem/stromal cells

et al. 2019

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Mesenchymal Stem/Stromal Cells (MSCs) have been widely considered as a promising source of cells for tissue regeneration. Among other stem cells, they are characterized by a high osteogenic potential. Intensive studies in this field had shown that even if basic osteogenic differentiation is relatively simple, its clinical application requires more sophisticated approaches to prepare effective and safe cell therapy products. The aim of this review is to underline biological, physical and chemical factors which play a crucial role in osteogenic differentiation of MSCs. Existence of two distinct mechanisms of ossification (intramembranous and endochondral) indicate that choosing a proper source of MSCs may be critical for successful regeneration of a particular bone type. In this context, Dental Pulp Stem Cells representing a group of MSCs and originating from neural crest ( a structure responsible for development of cranial bones) are considered as the most promising for skull bone defect repair. Factors which facilitate osteogenic differentiation of MSCs include changes in forces exerted on cells during development. Thus, culturing of cells in hydrogels or on biocompatible three-dimensional scaffolds improves osteogenic differentiation of MSCs by both, the mechanotransductive and chemical impact on cells. Moreover, atmospheric oxygen concentration routinely used for cell cultures in vitro does not correspond to lower oxygen concentration present in stem cell niches. A decrease in oxygen concentration allows to create more physiological cell culture conditions, mimicking the ones in stem cell niches, which promote the MSCs stemness. Altogether, factors discussed in this review provide exciting opportunities to boost MSCs propagation and osteogenic differentiation which is crucial for successful clinical applications.

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Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head

Cited by 40 publications

References 62 publications

Clinical and Radiographic Alterations in Bilateral Avascular Necrosis of the Femoral Head Following Laser Acupuncture: A Case Report

Clinical and Radiographic Alterations in Bilateral Avascular Necrosis of the Femoral Head Following Laser Acupuncture: A Case Report

Prevention of glucocorticoid-associated osteonecrosis by intravenous administration of mesenchymal stem cells in a rabbit model

Impact of developmental origin, niche mechanics and oxygen availability on osteogenic differentiation capacity of mesenchymal stem/stromal cells

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