Our Fat Future: Translating Adipose Stem Cell Therapy

Mesenchymal stem cells (MSCs) represent a potentially revolutionary therapy for a wide variety of pediatric diseases, but the optimal cell‐based therapeutics for such diversity have not yet been specified. The published clinical trials for pediatric pulmonary, cardiac, orthopedic, endocrine, neurologic, and hematologic diseases provide evidence that MSCs are indeed efficacious, but the significant heterogeneity in therapeutic approaches between studies raises new questions. The purpose of this review is to stimulate new preclinical and clinical trials to investigate these factors. First, we discuss recent clinical trials for pediatric diseases studying MSCs obtained from bone marrow, umbilical cord and umbilical cord blood, placenta, amniotic fluid, and adipose tissue. We then identify factors, some unique to pediatrics, which must be examined to optimize therapeutic efficacy, including route of administration, dose, timing of administration, the role of ex vivo differentiation, cell culture techniques, donor factors, host factors, and the immunologic implications of allogeneic therapy. Finally, we discuss some of the practicalities of bringing cell‐based therapy into the clinic, including regulatory and manufacturing considerations. The aim of this review is to inform future studies seeking to maximize therapeutic efficacy for each disease and for each patient. Stem Cells Translational Medicine 2017;6:539–565

Section: Clinical Studies Of Msc Therapymentioning

confidence: 99%

Concise Review: Mesenchymal Stem Cell Therapy for Pediatric Disease: Perspectives on Success and Potential Improvements

Nitkin

Bonfield

2016

“…Adipose tissue has been identified as an alternative and abundant source of stromal progenitors, typically referred to as adipose stromal cells (ASC) [10]. Human ASC display several distinct translational advantages over mesenchymal stromal cells (MSC) from other tissues, such as bone marrow or umbilical cord, and have been used in a rapidly growing number of clinical trials [11]. Moreover, their biological properties and osteoprogenitor nature are generally recognized to be distinct from those of BMSC [8].…”

Section: Introductionmentioning

confidence: 99%

Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification

Osinga

Maggio

Todorov

et al. 2016

Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a variety of settings for mimicking ECO during development, physiology, or pathology (e.g., to investigate the role of BMPs, their receptors, and signaling pathways). The findings have also translational relevance in the field of bone regeneration, which, despite several advances in the domains of materials and surgical techniques, still faces various limitations before being introduced in the routine clinical practice.

“…Variability among stem cells isolated from different donors is a well‐documented barrier to the clinical translation of autologous stem cell therapies . Human adipose stem cells (hASCs) are an attractive autologous stem cell source for tissue engineering and regenerative medicine applications because of their relative ease of isolation, multipotent differentiation capacity, and immunocompatibility .…”

Section: Introductionmentioning

confidence: 99%

Electrical Cell-Substrate Impedance Spectroscopy Can Monitor Age-Grouped Human Adipose Stem Cell Variability During Osteogenic Differentiation

Nordberg

Zhang

Griffith

et al. 2016

Self Cite

Human adipose stem cells (hASCs) are an attractive cell source for bone tissue engineering applications. However, a critical issue to be addressed before widespread hASC clinical translation is the dramatic variability in proliferative capacity and osteogenic potential among hASCs isolated from different donors. The goal of this study was to test our hypothesis that electrical cell‐substrate impedance spectroscopy (ECIS) could track complex bioimpedance patterns of hASCs throughout proliferation and osteogenic differentiation to better understand and predict variability among hASC populations. Superlots composed of hASCs from young (aged 24–36 years), middle‐aged (aged 48–55 years), and elderly (aged 60–81 years) donors were seeded on gold electrode arrays. Complex impedance measurements were taken throughout proliferation and osteogenic differentiation. During osteogenic differentiation, four impedance phases were identified: increase, primary stabilization, drop phase, and secondary stabilization. Matrix deposition was first observed 48–96 hours after the impedance maximum, indicating, for the first time, that ECIS can identify morphological changes that correspond to late‐stage osteogenic differentiation. The impedance maximum was observed at day 10.0 in young, day 6.1 in middle‐aged, and day 1.3 in elderly hASCs, suggesting that hASCs from younger donors require a longer time to differentiate than do hASCs from older donors, but young hASCs proliferated more and accreted more calcium long‐term. This is the first study to use ECIS to predict osteogenic potential of multiple hASC populations and to show that donor age may temporally control onset of osteogenesis. These findings could be critical for development of patient‐specific bone tissue engineering and regenerative medicine therapies. Stem Cells Translational Medicine 2017;6:502–511