Dysfunctional stem and progenitor cells impair fracture healing with age

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly

Soft Tissue Manipulation May Attenuate Inflammation, Modulate Pain, and Improve Gait in Conscious Rodents With Induced Low Back Pain

Introduction: Low back pain (LBP) is common in warfighters. Noninvasive interventions are necessary to expedite return-to-function. Soft tissue manipulation, for example, massage, is a method used to treat LBP. Instrument-assisted soft tissue manipulation (IASTM) uses a rigid device to mobilize the tissue. This study explored the effects of IASTM on pain, function, and biomarkers. Methods: Sprague-Dawley rats (n = 44) were randomized to groups (n = 6/grp): (A) cage control; (B) 3 days (3d) postinjury (inj), untreated; (C) 3d inj, < 30-minute post-IASTM treatment; (D) 3d inj, 2 hours (2h) post-IASTM; (E) 14 days (14d) inj, untreated; (F) 14d inj, < 30-minute post-IASTM; and (G) 14d inj, 2h post-IASTM. Researchers induced unilateral LBP in Sprague-Dawley rats using complete Freund's adjuvant injection. Conscious rodents received IASTM for 5 min/session once at 3 days or 3×/week × 2weeks (6× total) over 14 days. Biomarker plasma levels were determined in all groups, while behavioral outcomes were assessed in two groups, D and G, at three time points: before injury, pre-, and post-IASTM treatment. Circulating mesenchymal stem cell levels were assessed using flow cytometry and cytokine plasma levels assayed. Results: The back pressure pain threshold (PPT) lowered bilaterally at 3 days postinjury (P < .05), suggesting increased pain sensitivity. IASTM treatment lowered PPT more on the injured side (15.8%; P < 0.05). At 14 days, back PPT remained lower but similar side to side. At 3 days, paw PPT increased 34.6% in the contralateral rear limb following treatment (P < .01). Grip strength did not vary significantly. Gait coupling patterns improved significantly (P < .05). Circulating mesenchymal stem cell levels altered significantly postinjury but not with treatment. Neuropeptide Y plasma levels increased significantly at 3 days, 2h post-IASTM (53.2%) (P < .05). Interleukin-6 and tumor necrosis factor-alpha did not vary significantly. At 14 days, regulated on activation, normal T cell expressed and secreted decreased significantly <30-minute post-IASTM (96.1%, P < .002), while IL-10 trended upward at 2h (53.1%; P = .86). Conclusions: LBP increased pain sensitivity and diminished function. IASTM treatment increased pain sensitization acutely in the back but significantly reduced pain sensitivity in the contralateral rear paw. Findings suggest IASTM may positively influence pain modulation and inflammation while improving gait patterns. Soft tissue manipulation may be beneficial as a conservative treatment option for LBP