Adipose-derived stromal cells: Their identity and uses in clinical trials, an update

In adults, adipose tissue is abundant and can be easily sampled using liposuction. Largely involved in obesity and associated metabolic disorders, it is now described as a reservoir of immature stromal cells. These cells, called adipose-derived stromal cells (ADSCs) must be distinguished from the crude stromal vascular fraction (SVF) obtained after digestion of adipose tissue. ADSCs share many features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but they also display some specific features, including a greater angiogenic potential. Their angiogenic properties as well as their paracrine activity suggest a putative tumor-promoting role for ADSCs although contradictory data have been published on this issue. Both SVF cells and ADSCs are currently being investigated in clinical trials in several fields (chronic inflammation, ischemic diseases, etc. ). Apart from a phase Ⅲ trial on the treatment of fistula,most of these are in phaseⅠand use autologous cells. In the near future, the end results of these trials should provide a great deal of data on the safety of ADSC use.     

Adipose-derived mesenchymal stem cells stereotactic transplantation alleviate brain edema from intracerebral hemorrhage

Adipose-derived mesenchymal stromal cells (ADSCs) exhibited high potential in tissue repair and regeneration, and it has been proved that ADSCs could protect brain cells from apoptosis and maintaining blood-brain barrier stability after cerebral vascular disease. In this study, we evaluated the therapeutic potential and mechanism of ADSCs stereotactic transplantation in intracerebral hemorrhage (ICH) mice model and hemin-treated astrocytes. Mice were divided into three groups: sham group, ICH + PBS group, and ICH + ADSC group. Mice in ICH + ADSC group received ADSCs cell suspension stereotactic transplantation into the area beside the bleeding region. Astrocytes were divided into three groups: control group, hemin group, and hemin + ADSC group. Astrocytes in hemin + ADSC group were cultured in ADSCs-astrocyte no-contact coculture system and treated with 30 μM hemin solution. The results showed that ADSCs stereotactic transplantation improved functional outcomes and reduced cell apoptosis after ICH. Moreover, ADSCs stereotactic transplantation could alleviate brain edema and inflammation and AQP4 protein expression contributed to the alleviation of brain edema. In addition, mitogen-activated protein kinase (MAPK) pathways, including p38/MAPK pathway and c-Jun N-terminal kinase pathway, were involved in AQP4 modulation by ADSCs transplantation in ICH. In conclusion, ADSCs transplantation could alleviate the nervous tissue injury, reduce cell apoptosis, and relieve brain edema in ICH. And the edema regulation effect of ADSCs transplantation is associated with inhibition of inflammation and AQP4 protein expression.     

Advances in stem cell therapy for the lower urinary tract

Lower urinary tract diseases are emotionally and financially burdensome to the individual and society. Current treatments are ineffective or symptomatic. Conversely, stem cells (SCs) are regenerative and may offer long-term solutions. Among the different types of SCs, bone marrow SCs (BMSCs) and skeletal muscle-derived SCs (SkMSCs) have received the most attention in pre-clinical and clinical trial studies concerning the lower urinary tract. In particular, clinical trials with SkMSCs for stress urinary incontinence have demonstrated impressive efficacy. However, both SkMSCs and BMSCs are difficult to obtain in quantity and therefore neither is optimal for the eventual implementation of SC therapy. On the other hand, adipose tissue-derived SCs (ADSCs) can be easily and abundantly obtained from "discarded" adipose tissue. Moreover, in several head-on comparison studies, ADSCs have demonstrated equal or superior therapeutic potential compared to BMSCs. Therefore, across several different medical disciplines, including urology, ADSC research is gaining wide attention. For the regeneration of bladder tissues, possible differentiation of ADSCs into bladder smooth muscle and epithelial cells has been demonstrated. For the treatment of bladder diseases, specifically hyperlipidemia and associated overactive bladder, ADSCs have also demonstrated efficacy. For the treatment of urethral sphincter dysfunction associated with birth trauma and hormonal deficiency, ADSC therapy was also beneficial. Finally, ADSCs were able to restore erectile function in various types of erectile dysfunction (ED), including those associated with diabetes, hyperlipidemia, and nerve injuries. Thus, ADSCs have demonstrated remarkable therapeutic potentials for the lower urinary tract.     

Differentiation of human adipose derived stem cells into Leydig‐like cells with molecular compounds

Leydig cells (LCs) are the primary source of testosterone in the testis, and testosterone deficiency caused by LC functional degeneration can lead to male reproductive dysfunction. LC replacement transplantation is a very promising approach for this disease therapy. Here, we report that human adipose derived stem cells (ADSCs) can be differentiated into Leydig‐like cells using a novel differentiation method based on molecular compounds. The isolated human ADSCs expressed positive CD29, CD44, CD59 and CD105, negative CD34, CD45 and HLA‐DR using flow cytometry, and had the capacity of adipogenic and osteogenic differentiation. ADSCs derived Leydig‐like cells (ADSC‐LCs) acquired testosterone synthesis capabilities, and positively expressed LC lineage‐specific markers LHCGR, STAR, SCARB1, SF‐1, CYP11A1, CYP17A1, HSD3B1 and HSD17B3 as well as negatively expressed ADSC specific markers CD29, CD44, CD59 and CD105. When ADSC‐LCs labelled with lipophilic red dye (PKH26) were injected into rat testes which were selectively eliminated endogenous LCs using ethylene dimethanesulfonate (EDS, 75 mg/kg), the transplanted ADSC‐LCs could survive and function in the interstitium of testes, and accelerate the recovery of blood testosterone levels and testis weights. These results demonstrated that ADSCs could be differentiated into Leydig‐like cells by few defined molecular compounds, which might lay the foundation for further clinical application of ADSC‐LC transplantation therapy.     

Activin B regulates adipose-derived mesenchymal stem cells to promote skin wound healing via activation of the MAPK signaling pathway

Adipose-derived stem cells (ADSCs) are multipotent stromal cells that can differentiate into a variety of cell types, including skin cells, and they can provide an abundant source of cells for skin tissue engineering and skin wound healing. The purpose of this study is to explore the therapeutic effects of activin B in combination with ADSCs and the possible signaling mechanism. In this study, we found that activin B was able to promote ADSC migration by inducing actin stress fiber formation in vitro. In vivo, activin B in combination with ADSCs was capable of enhancing α-SMA expression and wound closure. This combined treatment also promoted fibroblast and keratinocyte proliferation and accelerated re-epithelialization and collagen deposition. Moreover, activin B in combination with ADSCs boosted angiogenesis in the wound area. Further study of the mechanism revealed that activation of JNK and ERK signaling, but not p38 signaling, were required for activin B-induced ADSC actin stress fiber formation and cell migration. These results showed that activin B was able to activate JNK and ERK signaling pathways to induce actin stress fiber formation and ADSC migration to promote wound healing. These results suggest that combined treatment with activin B and ADSCs is a promising therapeutic strategy for the management of serious skin wounds.     

脂肪干细胞治疗心肌梗死的机制与新策略

介绍脂肪干细胞（ADSCs）治疗心肌梗死机制及用于提高心肌梗死治疗效果的新策略。广泛查阅近年关于ADSCs用于治疗心肌梗死的基础与临床实验研究文献,并进行整理、综合与分析。ADSCs移植治疗心肌梗死的机制研究取得了一定的进展,其机制主要包括分化为心肌细胞、参与梗死区血管形成、通过旁分泌功能改善梗死区微环境等。对ADSCs进行缺氧耐受预处理、使用新型生物材料、联合细胞因子以及药物等,可以大大提高移植细胞的存活率,促进细胞的增殖与分化,改善心肌梗死治疗效果,加快心脏功能的恢复。ADSCs可能通过多种机制发挥治疗心肌梗死的作用,进一步提高移植细胞成活率和性能稳定性是增加ADSCs治疗心肌梗死效果的关键。随着研究的不断深入,ADSCs可能为未来心肌梗死的临床治疗带来新的希望。     

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental model shave been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells(ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury(PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair.     

Adipose-derived stromal cell in regenerative medicine: A review

The application of appropriate cell origin for utilizing inregenerative medicine is the major issue. Various kinds of stem cells have been used for the tissue engineering and regenerative medicine. Such as, several stromal cells have been employed as treat option for regenerative medicine. For example, human bone marrow-derived stromal cells and adipose-derived stromal cells(ADSCs) are used in cell-based therapy. Data relating to the stem cell therapy and processes associated with ADSC has developed remarkably in the past 10 years. As medical options, both the stromal vascular and ADSC suggests good opportunity as marvelous cell-based therapeutics. The some biological features are the main factors that impact the regenerative activity of ADSCs, including the modulation of the cellular immune system properties and secretion of bioactive proteins such as cytokines, chemokines and growth factors, as well as their intrinsic anti-ulcer and anti-inflammatory potential. A variety of diseases have been treated by ADSCs, and it is not surprising that there has been great interest in the possibility that ADSCs might be used as therapeutic strategy to improve a wider range of diseases. This is especially important when it is remembered that routine therapeutic methods are not completely effective in treat of diseases. Here, it was discuss about applications of ADSC to colitis, liver failure, diabetes mellitus, multiple sclerosis, orthopaedic disorders, hair loss, fertility problems, and salivary gland damage.     

Murine Adipose Tissue-Derived Stromal Cell Apoptosis and Susceptibility to Oxidative Stress In Vitro Are Regulated by Genetic Background

Adipose tissue-derived stromal cells (ADSCs) are of interest for regenerative medicine as they are isolated easily and can differentiate into multiple cell lineages. Studies of their in vitro proliferation, survival, and differentiation are common; however, genetic effects on these phenotypes remain unknown. To test if these phenotypes are genetically regulated, ADSCs were isolated from three genetically diverse inbred mouse strains- C57BL/6J (B6), BALB/cByJ (BALB), and DBA/2J (D2)- in which genetic regulation of hematopoietic stem function is well known. ADSCs from all three strains differentiated into osteogenic and chondrogenic lineages in vitro. ADSCs from BALB grew least well in vitro, probably due to apoptotic cell death after several days in culture. BALB ADSCs were also the most susceptible to the free radical inducers menadione and H₂O₂. ADSCs from the three possible F1 hybrids were employed to further define genetic regulation of ADSC phenotypes. D2, but not B6, alleles stimulated ADSC expansion in BALB cells. In contrast, B6, but not D2, alleles rescued BALB H₂O₂ resistance. We conclude that low oxidative stress resistance does not limit BALB ADSC growth in vitro, as these phenotypes are genetically regulated independently. In addition, ADSCs from these strains are an appropriate model system to investigate genetic regulation of ADSC apoptosis and stress resistance in future studies. Such investigations are essential to optimize cell expansion and differentiation and thus, potential for regenerative medicine.     

CD4+ Cells Regulate Fibrosis and Lymphangiogenesis in Response to Lymphatic Fluid Stasis

Introduction

Lymphedema is a chronic disorder that occurs commonly after lymph node removal for cancer treatment and is characterized by swelling, fibrosis, inflammation, and adipose deposition. Although previous histological studies have investigated inflammatory changes that occur in lymphedema, the precise cellular make up of the inflammatory infiltrate remains unknown. It is also unclear if this inflammatory response plays a causal role in the pathology of lymphedema. The purpose of this study was therefore to characterize the inflammatory response to lymphatic stasis and determine if these responses are necessary for the pathological changes that occur in lymphedema.

Methods

We used mouse-tail lymphedema and axillary lymph node dissection (ANLD) models in order to study tissue inflammatory changes. Single cell suspensions were created and analyzed using multi-color flow cytometry to identify individual cell types. We utilized antibody depletion techniques to analyze the causal role of CD4+, CD8+, and CD25+ cells in the regulation of inflammation, fibrosis, adipose deposition, and lymphangiogenesis.

Results

Lymphedema in the mouse-tail resulted in a mixed inflammatory cell response with significant increases in T-helper, T-regulatory, neutrophils, macrophages, and dendritic cell populations. Interestingly, we found that ALND resulted in significant increases in T-helper cells suggesting that these adaptive immune responses precede changes in macrophage and dendritic cell infiltration. In support of this we found that depletion of CD4+, but not CD8 or CD25+ cells, significantly decreased tail lymphedema, inflammation, fibrosis, and adipose deposition. In addition, depletion of CD4+ cells significantly increased lymphangiogenesis both in our tail model and also in an inflammatory lymphangiogenesis model.

Conclusions

Lymphedema and lymphatic stasis result in CD4+ cell inflammation and infiltration of mature T-helper cells. Loss of CD4+ but not CD8+ or CD25+ cell inflammation markedly decreases the pathological changes associated with lymphedema. In addition, CD4+ cells regulate lymphangiogenesis during wound repair and inflammatory lymphangiogenesis.     

Current applications of adipose-derived stem cells and their future perspectives

Adult stem cells have a great potential to treat various diseases. For these cell-based therapies, adipose-derived stem cells(ADSCs) are one of the most promising stem cell types, including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs). ESCs and iPSCs have taken center stage due to their pluripotency. However, ESCs and iPSCs have limitations in ethical issues and in identification of characteristics, respectively. Unlike ESCs and iPSCs, ADSCs do not have such limitations and are not only easily obtained but also uniquely expandable. ADSCs can differentiate into adipocytes, osteoblasts, chondrocytes, myocytes and neurons under specific differentiation conditions, and these kinds of differentiation potential of ADSCs could be applied in regenerative medicine e.g., skin reconstruction, bone and cartilage formation, etc. In this review, the current status of ADSC isolation, differentiation and their therapeutic applications are discussed.     

An experimental model for chronic lymphedema

Although a multitude of operations exist for the treatment of lymphedema, none is highly successful. An experimental model that reliably and easily produces chronic lymphedema in an extremity would be useful to study treatments in a controlled and comparative manner and would enhance our understanding of the physiology and treatment of lymphedema. Many models that simulate clinical lymphedema have been described, but they suffer from cumbersome protocols, high laboratory costs, and an inconsistent yield of permanent lymphedema. We describe an experimental model for chronic lymphedema in the lower extremity of the rat that creates a lymphatic block in the groin induced by radiation treatment and one operation--surgical division of the superficial and deep lymphatics. All animals develop stable chronic lymphedema of the lower extremity within days of operation, with swelling that persists for at least 9 months. A mortality rate of 8 percent was associated with this technique. Methods for quantification of limb swelling are described, as is analysis of the lymphatic block by lymphoscintigraphic imaging of lymph channels and nodes. This model has the advantages of simplicity of technique, cost-effective use of rodent subjects, reproducibility of lymphedema, and quantification of results.     

GJC2 Missense Mutations Cause Human Lymphedema

Lymphedema is the clinical manifestation of defects in lymphatic structure or function. Mutations identified in genes regulating lymphatic development result in inherited lymphedema. No mutations have yet been identified in genes mediating lymphatic function that result in inherited lymphedema. Survey microarray studies comparing lymphatic and blood endothelial cells identified expression of several connexins in lymphatic endothelial cells. Additionally, gap junctions are implicated in maintaining lymphatic flow. By sequencing GJA1, GJA4, and GJC2 in a group of families with dominantly inherited lymphedema, we identified six probands with unique missense mutations in GJC2 (encoding connexin [Cx] 47). Two larger families cosegregate lymphedema and GJC2 mutation (LOD score = 6.5). We hypothesize that missense mutations in GJC2 alter gap junction function and disrupt lymphatic flow. Until now, GJC2 mutations were only thought to cause dysmyelination, with primary expression of Cx47 limited to the central nervous system. The identification of GJC2 mutations as a cause of primary lymphedema raises the possibility of novel gap-junction-modifying agents as potential therapy for some forms of lymphedema.     

Current applications of adipose-derived stem cells and their future perspectives简

Adult stem cells have a great potential to treat various diseases. For these cell-based therapies, adipose-derived stem cells (ADSCs) are one of the most promising stem cell types, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs and iPSCs have taken center stage due to their pluripotency. However, ESCs and iPSCs have limitations in ethical issues and in identification of characteristics, respectively. Unlike ESCs and iPSCs, ADSCs do not have such limitations and are not only easily obtained but also uniquely expandable. ADSCs can differentiate into adipocytes, osteoblasts, chondrocytes, myocytes and neurons under specific differentiation conditions, and these kinds of differentiation potential of ADSCs could be applied in regenerative medicine e.g., skin reconstruction, bone and cartilage formation, etc. In this review, the current status of ADSC isolation, differentiation and their therapeutic applications are discussed.     

脂肪干细胞的研究进展

成体干细胞包括多能诱导干细胞、胚胎干细胞、脐带血干细胞、脂肪干细胞等,其中脂肪干细胞因其取材方便,无伦理限制,且能诱导成多胚层细胞而成为最有应用前景的成体干细胞之一。脂肪干细胞可以诱导分化为脂肪细胞、骨细胞、软骨细胞、肌细胞和神经元,在特定的条件下,可以构建皮肤,骨和软骨组织工程,是多种组织工程的理想种子细胞,有非常重要的研究和应用价值。本文综述了ADSC的分离培养、诱导分化,并着重对脂肪干细胞在组织工程临床应用方面的最新发展进行了阐述,以期为深入研究脂肪干细胞提供理论基础。     

Histological changes induced by Polyglycolic-Acid (PGA) scaffolds seeded with autologous adipose or muscle-derived stem cells when implanted on rabbit bladder

Purpose: To evaluate the morphological and histological changes induced by PGA scaffold seeded with autologous adipose or muscle derived stem cells implanted on rabbit bladder wall. Material and Methods: Adipose derived stem cells (ADSCs) were obtained from the inguinal fat of eight rabbits and muscle derived stem cells (MDSCs) from the anterior tibial muscle of other eight rabbits. After culture and isolation, the cells were stained with Vybrant Red CM DiI and then implanted at third passage. Two PGA scaffolds were implanted on the bladder submucosa of each animal. On the right bladder side was implanted unseeded PGA scaffold while on the left side was implanted ADSCs or skeletal MDSCs seeded PGA scaffold. ADSCs were implanted in eight animals and MDSC in other eight animals. The animals were sacrificed at four and eight weeks. Histological evaluation was performed with Hematoxylin and Eosin, Masson's Trichrome and smooth muscle α-actin. Results: We observed a mild inflammatory response in all the three groups. Seeded scaffolds induced higher lymphocytes and lower polimorphonuclear migration than controls. Fibrosis was more pronounced in the control groups. Smooth muscle α-actin was positive only in ADSC and MDSC seeded scaffolds. At four and eight weeks ADCSs and skeletal MDSCs labeled cells were found at the implant sites. Conclusions: The implantation of PGA scaffolds seeded with ADSC and MDSC induced less fibrosis than control and smooth muscle regeneration.     

HIF1A/miR-20a-5p/TGFβ1 axis modulates adipose-derived stem cells in a paracrine manner to affect the angiogenesis of human dermal microvascular endothelial cells

Angiogenic cytokines secreted by the adipose-derived stem cells (ADSCs) might promote the angiogenesis of endothelial cells. In the present study, we hypothesize that miR-20a targets TGFB1 to modulate the transforming growth factor β1 (TGFβ1) secretion by ADSCs, therefore affecting the angiogenesis. We found that hypoxia-inducible factor 1A (HIF1A) and TGFβ1 expressions were increased by hypoxia, accompanied with promoted ADSC cell viability. Incubation with conditioned medium from ADSCs treated with hypoxia significantly enhanced the angiogenesis capacity of human dermal microvascular endothelial cells (HDMECs), while TGFB1-silenced ADSCs medium significantly reverses HDMECs angiogenesis. miR-20a suppresses the expression of TGFB1 and secretion of TGFβ1 by ADSCs via binding to its 3′untranslated region, therefore modulating the HDMEC angiogenesis via affecting the paracrine from ADSCs; the effects of miR-20a-overexpressed conditioned medium on HDMEC angiogenesis were significantly reversed by TGFB1-overexpressed conditioned medium. Finally, HIF1A suppressed the expression of miR-20a via targeting its promoter region, subsequently promoting the paracrine from ADSCs and HDMEC angiogenesis.     

Transplantation of Mesenchymal Cells Improves Peripheral Limb Ischemia in Diabetic Rats

Adipose tissue-derived mesenchymal stromal cells (ADSCs) are a prominent cellular source for regenerative medicine. We tested whether transplantation of ADSCs into the ischemic muscular tissue of diabetic animals would attenuate impaired cell metabolism and microcirculatory function. We induced unilateral hind limb ischemia in male streptozotocin-treated rats and nondiabetic controls. One day after femoral artery ligation, six rats per group were intramuscularly injected allogeneic ADSCs (10⁶–10⁷–10⁸ cells/mL); or conditioned media from ADSC cultures (CM); or saline; or allogeneic fibroblasts (10⁷ cells/mL); or nonconditioned medium. Rats underwent magnetic resonance angiography; short time inversion recovery (STIR) edema-weighed imaging; proton MR spectroscopy (¹H-MRS); immunoblotting and immunofluorescence on both hind limbs for 4 weeks. T₁-weighted and STIR images showed tissue swelling and signal hyperintensity, respectively, in the ischemic tissue. The mean total ratio of creatine/water for the occluded limbs was significantly lower than for the nonoccluded limbs in both nondiabetic and diabetic rats. ADSC and CM groups had greater recovery of tCr/water in ischemic limbs in both diabetic and nondiabetic rats, with increased expression of α-sarcomeric actinin, vascular endothelial growth factor and hepatocyte growth factor, as well as increased vessel density. ADSCs improve ischemic muscle metabolism and increase neovasculogenesis in diabetic rats.     

Histological changes induced by Polyglycolic-Acid (PGA) scaffolds seeded with autologous adipose or muscle-derived stem cells when implanted on rabbit bladder

Purpose: To evaluate the morphological and histological changes induced by PGA scaffold seeded with autologous adipose or muscle derived stem cells implanted on rabbit bladder wall. Material and Methods: Adipose derived stem cells (ADSCs) were obtained from the inguinal fat of eight rabbits and muscle derived stem cells (MDSCs) from the anterior tibial muscle of other eight rabbits. After culture and isolation, the cells were stained with Vybrant Red CM DiI and then implanted at third passage. Two PGA scaffolds were implanted on the bladder submucosa of each animal. On the right bladder side was implanted unseeded PGA scaffold while on the left side was implanted ADSCs or skeletal MDSCs seeded PGA scaffold. ADSCs were implanted in eight animals and MDSC in other eight animals. The animals were sacrificed at four and eight weeks. Histological evaluation was performed with Hematoxylin and Eosin, Masson's Trichrome and smooth muscle α-actin. Results: We observed a mild inflammatory response in all the three groups. Seeded scaffolds induced higher lymphocytes and lower polimorphonuclear migration than controls. Fibrosis was more pronounced in the control groups. Smooth muscle α-actin was positive only in ADSC and MDSC seeded scaffolds. At four and eight weeks ADCSs and skeletal MDSCs labeled cells were found at the implant sites. Conclusions: The implantation of PGA scaffolds seeded with ADSC and MDSC induced less fibrosis than control and smooth muscle regeneration.     

Choosing the right type of serum for different applications of human adipose tissue–derived stem cells: influence on proliferation and differentiation abilities

Background aimsAdipose tissue–derived stem cells (ADSCs) are thought to have great potential in regenerative medicine. A xenoprotein-free culture and handling system is desirable. To date, there is only little and contradictory information about the influence of the different types of human serum on ADSC proliferation and differentiation.MethodsFirst, ADSCs were cultured in media containing regular human serum (HS plus) or fetal calf serum (FCS plus) with supplementation of growth factors for three passages. During passage 4, ADSC proliferative activity and adipogenic, osteogenic and chondrogenic differentiation ability was quantified. Second, ADSCs were cultured with three different human sera (regular human serum [HS], human serum from platelet-poor plasma [SPPP] or human serum from platelet-rich plasma [SPRP]) without supplementation of platelet-derived growth factor and assessed accordingly. The growth factor content of the different types of human sera was determined by means of multiplex protein assay and enzyme-linked immunosorbent assay.ResultsThe different sera did not affect ADSC doubling time significantly (P < 0.05). Specific glycerol-3-phosphat-dehydrogenase activity was significantly lower in cultures with SPRP (P < 0.01) compared with the other media compositions. Extracellular calcium deposition was significantly higher in cells differentiated in cultures with HS or SPPP compared with those with SPRP, HS plus or FCS (P < 0.01). Glycosaminoglycan content and collagen 2 were highest in cells cultured with SPRP (P < 0.001).ConclusionsCulturing ADSCs in human serum appears to be a reasonable and efficient alternative compared with FCS. With respect to the outcome of a sighted clinical application, it appears to be feasible to handle the cells in a serum suitable for the intended later use.