Adipose-Derived Stem Cells as a Tool in Cell-Based Therapies

Abstract

Recent development in stem cell isolation methods and expansion under laboratory conditions create an opportunity to use those aforementioned cells in tissue engineering and regenerative medicine. Particular attention is drawn towards mesenchymal stem cells (MSCs) being multipotent progenitors exhibiting several unique characteristics, including high proliferation potential, self-renewal abilities and multilineage differentiation into cells of mesodermal and non-mesodermal origin. High abundance of MSCs found in adipose tissue makes it a very attractive source of adult stem cells for further use in regenerative medicine applications. Despite immunomodulating properties of adipose-derived stem cells (ASCs) and a secretion of a wide variety of paracrine factors that facilitate tissue regeneration, effectiveness of stem cell therapy was not supported by the results of clinical trials. Lack of a single, universal stem cell marker, patient-to-patient variability, heterogeneity of ASC population combined with multiple widely different protocols of cell isolation and expansion hinder the ability to precisely identify and analyze biological properties of stem cells. The above issues contribute to conflicting data reported in literature. We will review the comprehensive information concerning characteristic features of ASCs. We will also review the regenerative potential and clinical application based on various clinical trials.

Efficacy of human HC016 cell transplants on neuroprotection and functional recovery in a rat model of acute spinal cord injury

“…As a result, a higher preservation of total myelin area was observed from as early as 14 dpi at the adjacent to epicentre rostro‐caudal spinal cord, with special emphasis on the ventrolateral tracts, which have been reported as highly involved on the compensatory circuitry behind functional recovery after SCI (Cao et al, ; Shucht, Raineteau, Schwab, & Fouad, ). In agreement with previous reports, these results suggest that one of the most relevant effects derived of early cell transplantation at the injured parenchyma is neuroprotection, as well as that the beneficial effects observed at long term would be most likely resulting from a paracrine trophic action rather than from a cellular replacement in the injured cord as alternatively suggested (Bajek et al, ; Salgado, Reis, Sousa, & Gimble, ; Z. Zhou et al, ). This is further supported by the reduced microglial reactivity observed caudally to the injury in the hHC016 group at 56 dpi, probably resulting from the lower incidence of secondary cell death and higher preservation of functional neural connections.…”

“…Among them, MSCs have received considerable interest because they can be easily isolated from a variety of different tissues and expanded with high efficiency, while showing potent anti‐inflammatory, antiapoptotic, angiogenic, and immunomodulatory activities in preclinical models (Dasari et al, ; Vawda & Fehlings, ). Therefore, MSCs have been widely assessed in clinical trials, showing promising although variable results on survival, integration, and functional recovery (Bajek et al, ; Y. H. Kim, Ha, & Kim, ; Oliveri, Bello, & Biering‐Sorensen, ; Shende & Subedi, ). Herein, bone marrow mesenchymal stem cells have been commonly considered as the first source of MSCs for SCI treatment.…”

“…However, in the last years, several studies in animal models of SCI have demonstrated comparable results with AMSCs (Im, ; Kolar, Kingham, Novikova, Wiberg, & Novikov, ; Takahashi et al, ; Z. Zhou et al, ) which otherwise are much easier to isolate from healthy donors and in larger amounts than from bone marrow (Strioga, Viswanahatan, Darinskas, Slaby, & Michalek, ). These properties make of them a very attractive cell therapy alternative for SCI, as highlights the four clinical trials using these cells in subacute or chronic stages after SCI currently underway (Bajek et al, ).…”

“…In particular, adipose MSCs (AMSCs) are easily obtained and have excellent expansion capacities, as well as a unique immunomodulatory and paracrine competence able to modulate many of the detrimental effects elicited after acute SCI (Mazini, Rochette, Amine, & Malka, ; Menezes et al, ; Takahashi et al, ). These effects together with a proven preclinical efficacy and safety profile have paved the way for the clinical assessment of AMSCs in a variety of trials (Bajek et al, ; Hur et al, ; Jin et al, ).…”

Multipotency and secretome: the mechanisms behind the regenerative potential of adipose-derived stem cells

“…These culture expanded ASCs are positive for CD34 (could be negative in further expansions), CD44, CD73, CD90 and CD105 like other MSCs and negative for CD31 and CD45 [ Figure 1]. [10,11] ASCs are different from BM-MSCs since they are positive for CD36 (GPIIIb) and negative for CD106 (vascular cell adhesion molecule-1). [12,13] It is also known that ASCs lose CD34 expression over time with consecutive passaging.…”