Adipose mesenchymal stem cells from osteoporotic donors preserve functionality and modulate systemic inflammatory microenvironment in osteoporotic cytotherapy

Abstract

Maintenance of bone homeostasis against diseased microenvironments remains as a major challenge.Recently, mesenchymal stem cells (MSCs) have been unravelled as potent microenvironmental modulators, the systemic infusion of which in cytotherapy can prevent or rescue extensive bone loss via anti-inflammation. However, MSCs also accept microenvironmental regulations; particularly, MSCs from bone marrow (BMMSCs) are prone to pathological microenvironmental factors of bone. In this study, we discovered that BMMSCs from osteoporotic donors of ovariectomized (OVX) mice lost their anti-inflammatory capability and failed to prevent bone loss when infused back into OVX recipients. Nevertheless, MSCs from adipose tissues (ADMSCs) preserved their anti-inflammatory capacity, despite diseased microenvironments of OVX donors, and continued to show protective effects on bone in OVX recipients. In the cellular level, the anti-inflammatory superiority of osteoporotic donor-derived ADMSCs over BMMSCs existed in their distinctive capability to induce T-cell apoptosis, which was molecularly attributed to retained expression levels of critical immunomodulatory genes. Furthermore, these functional discrepancies of BMMSCs and ADMSCs were due to differential stemness, energy metabolism and anti-oxidative defence system, underlying general disparity in their cellular states. Collectively, our findings optimize osteoporotic cytotherapy by using ADMSCs in resistance to and in modulation of diseased microenvironments.Maintenance of postnatal bone homeostasis requires dynamic bone remodelling balance carefully controlled by local and circulatory microenvironments 1,2 . In pathological conditions, microenvironmental alterations such as estrogen deficiency and the associated inflammation trigger extensive bone loss, the cure to which remains as an unfulfilled challenge in modern medicine [3][4][5] . In the recent decade, other than their putative role in keeping tissue homeostasis, mesenchymal stem cells (MSCs) have emerged as potent microenvironmental modulators, the systemic infusion of which exerts immense anti-inflammatory effects that benefit a variety of tissues/organs including bone 6,7 . Indeed, we and others have revealed the efficacy of systemic MSC therapy to restore bone remodelling in prevention or treatment of osteoporosis, via normalizing the diseased inflammatory microenvironments rather than exerting local effects by homing to osteoporotic region 8,9 . However, as reciprocal interactions, MSCs also

Photoreceptor protection by mesenchymal stem cell transplantation identifies exosomal MiR-21 as a therapeutic for retinal degeneration

“…It is recognized that MSCT maintains tissue homeostasis through either paracrine effects to establish beneficial microenvironments or through inhabitation in recipient tissues to replenish deficient cells [14,55]. After intravitreal transplantation, exogenous MSCs have been traced to remain in the vitreous body, in which no retinal incorporation has been reported [56][57][58].…”

A quantum thermometric sensing and analysis system using fluorescent nanodiamonds for the evaluation of living stem cell functions according to intracellular temperature

“…[1][2][3][4][5] Somatic stem cells have already been conrmed to show great safety, leading to various medical applications in regenerative medicine. In particular, adipose tissue-derived stem cells (ASCs) have recently attracted considerable attention as a multipotent stem cell source for regenerative medicine, 6,7 because large amounts of ASCs can be obtained using methods that are relatively easy to perform (e.g., lipoaspiration under local anesthesia) and because ASCs are known to produce large amounts of growth factors (e.g., hepatocyte growth factor [HGF] and vascular endothelial growth factor [VEGF]) in comparison to other somatic stem cells. [8][9][10] In addition, ASCs have the potential to self-renew and differentiate into many kinds of mesenchymal cells including adipocytes and osteocytes.…”

NDRG2 suppression as a molecular hallmark of photoreceptor-specific cell death in the mouse retina

“…Methyl thiazolyl tetrazolium (MTT)-based assay was used to determine cell viability, as stated before 73 , 74 . Briefly, after treatment by H 2 O 2 or MNU, or transfected with lentiviral vectors, cells were incubated with 20-μl 5 mg/ml MTT (MP Biomedicals, USA) for 4 h. The precipitates were extracted with 180-μl DMSO and the absorbance was measured at the optical density (OD) of 490 nm as the viability index.…”