Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head

Wyles, Cody C.; Houdek, Matthew T.; Crespo‐Diaz, Ruben; Norambuena, Germán A.; Stalboerger, Paul G.; Terzic, André; Behfar, Atta; Sierra, Rafael J.

doi:10.1007/s11999-015-4385-8

Cited by 51 publications

(36 citation statements)

References 41 publications

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“…Adipose-derived mesenchymal stem cells (ADSCs) have been suggested to be superior to BMSCs in some orthopedic applications (Wyles and others 2015). However, most studies of this type have been conducted in subjects less than 60 years of age.…”

Section: Treating Age-related Adipose Tissue Dysfunctionmentioning

confidence: 99%

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Palmer

Kirkland

2016

Experimental Gerontology

258

219

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Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies.

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Section: Treating Age-related Adipose Tissue Dysfunctionmentioning

confidence: 99%

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Palmer

Kirkland

2016

Experimental Gerontology

258

219

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“…Studies from OA and osteonecrosis patients have shown the most prominent impact on bone marrow-derived MSCs, with adipose-derived MSCs maintaining a greater level of functionality. 47 This observation may be secondary to the intense physiologic stress of the bone marrow microenvironment relative to comparatively quiescent adipose tissue. Differential dysfunction of MSCs by disease and tissue source has important implications for therapeutic implementation of cell transplantation therapies.…”

Section: Msc Derangements In Oa and Related Conditionsmentioning

confidence: 99%

Mesenchymal stem cell therapy for osteoarthritis: current perspectives

Wyles

Houdek

Behfar

et al. 2015

SCCAA

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Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.

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“…Although MSCs from different tissue sources have been shown to be similar in morphology and function, subtle differences may exist in their immunomodulatory profile which may be attributable to microenvironmental niche, method of harvest, or ontogenic age [24–26]. These differences may play a role in MSC reparative properties, and conflicting studies exist [27–29]. We therefore hypothesized that: (1) MSCs would increase survival and mesenteric perfusion, preserve intestinal histological architecture, and limit intestinal inflammation following intestinal ischemia and reperfusion injury (I/R), and 2) MSCs harvested from different source tissues would have equivalent protective properties to the intestine following I/R.…”

Section: Introductionmentioning

confidence: 99%

Harvest tissue source does not alter the protective power of stromal cell therapy after intestinal ischemia and reperfusion injury

Jensen

Manning

Khaneki³

et al. 2016

Journal of Surgical Research

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Background Transplantation of mesenchymal stromal cells (MSCs) may be a novel treatment for intestinal ischemia. The optimal stromal cell source that could yield maximal protection following injury, however, has not been identified. We hypothesized that: 1) MSCs would increase survival and mesenteric perfusion, preserve intestinal histological architecture, and limit inflammation following intestinal ischemia and reperfusion injury (I/R), and 2) MSCs harvested from different sources of tissue would have equivalent protective properties to the intestine following I/R. Methods Adult male mice were anesthetized and a midline laparotomy performed. The intestines were eviscerated, the small bowel mesenteric root identified, and baseline intestinal perfusion was determined using Laser Doppler Imaging (LDI). Intestinal ischemia was established by temporarily occluding the superior mesenteric artery for 60 minutes with a non-crushing clamp. Following ischemia, the clamp was removed and the intestines were allowed to recover. Prior to abdominal closure, 2 × 106 human umbilical (USCs), bone-marrow (BMSCs) derived MSCs, or keratinocytes in 250μl of phosphate-buffered saline (PBS) vehicle were injected into the peritoneum. Animals were allowed to recover for 12 or 24 hours (perfusion, histology, inflammatory studies), or 7 days (survival studies). Survival data was analyzed using log rank test. Perfusion was expressed as percentage of baseline and 12 and 24 hour data was analyzed using one way ANOVA and student’s t-test. Non parametric data was compared using Mann-Whitney-U test. A p-value of less than 0.05 was significant. Results All MSCs increased seven day survival following I/R and were superior to vehicle or keratinocytes (P<0.05). All MSCs increased mesenteric perfusion above vehicle at 12 and 24 hours following injury (P<0.05). All MSCs provided superior perfusion compared to keratinocytes at 24 hours post-injury (P<0.05). Administration of each MSC line improved intestinal histology after I/R (P<0.05). Multiple pro-inflammatory chemokines were down-regulated following application of MSCs suggesting a decreased inflammatory response following MSC therapy. Conclusion Transplantation of MSCs following intestinal I/R, irrespective of source tissue, significantly increases survival and mesenteric perfusion while limiting intestinal damage and inflammation. Further studies are needed to identify the mechanism that these cells utilize to promote improved outcomes following injury.

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Adipose-derived Mesenchymal Stem Cells Are Phenotypically Superior for Regeneration in the Setting of Osteonecrosis of the Femoral Head

Cited by 51 publications

References 41 publications

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Mesenchymal stem cell therapy for osteoarthritis: current perspectives

Harvest tissue source does not alter the protective power of stromal cell therapy after intestinal ischemia and reperfusion injury

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