The stromal vascular fraction (SVF) in adipose tissue contains a pool of various stem and progenitor cells, but the existence of hematopoietic stem and progenitor cells (HSPCs) in the SVF has not been seriously considered. We detected the presence of HSPCs in the SVF by phenotypically probing with Lin ؊ Sca-1 ؉ c-kit ؉ (LSK) and functionally confirming the presence using colony-forming cell assay and assessing the long-term multilineage reconstitution ability after SVF transplantation. The LSK population in the SVF was 0.004% plus or minus 0.001%, and 5 ؋ 10 5 freshly isolated SVF cells gave rise to 13 plus or minus 4 multilineage colonies. In addition, 0.15% plus or minus 0.03% of SVF cells was home to bone marrow (BM), especially near vascular and endosteal regions, 24 hours after blood transplantation. SVF transplantation was capable of generating a longterm (> 16 weeks), but variable extent (2.1%-32.1%) multilineage reconstitution in primary recipients, which was subsequently transferred to the secondary recipients by BM transplantation. All HSPCs within the SVF originated from the BM. Furthermore, the granulocyte-colonystimulating factor (G-CSF) mobilization of HSPCs from BM markedly elevated the number of phenotypic and functional HSPCs in the SVF, which induced a high efficiency long-term reconstitution in multilineage hematopoiesis in vivo. Our results provide compelling evidence that adipose tissue is a novel extramedullary tissue possessing phenotypic and functional HSPCs. (Blood. 2010;115:957-964) IntroductionHematopoietic stem and progenitor cells (HSPCs) in the complicated hierarchy of the hematopoietic system maintain themselves and generate many kinds of blood cells throughout life. To maintain their proper functioning, HSPCs reside in a special microenvironment called a niche. [1][2][3] Bone marrow (BM) is a dominant organ possessing a niche for HSPCs during adulthood. It is well known that a small fraction of HSPCs constantly circulate between the BM and peripheral blood without any stimulation. 4,5 The exiting and re-entering of HSPCs is mediated by interactions between several surface molecules, such as selectins and integrins. 1 In principle, on the way from peripheral blood back to the BM, HSPCs can settle down if the proper environment is provided. Supporting this concept, several extramedullary tissues were identified as HSPC-containing organs, including the liver, 6 spleen, 7 muscle, 8,9 and thoracic duct. 10 Among these organs, the liver and spleen are well-known locations for extramedullary hematopoiesis. 1 In both tissues, HSPCs reside close to sinusoidal endothelial cells, which may provide a preferential microenvironment. 6,11 The mechanism underlying HSPC maintenance in these extramedullary organs remains unclear, though the HSPCs still conserve their function properly. [6][7][8][9][10] Adipose tissues contain many different types of adult stem cells that can be used for therapeutic purposes, especially for tissue regeneration. 12 Adipose tissue is composed of lipid-filled mature ad...
Quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) using Tc-99m pertechnetate aids in evaluating salivary gland function. However, gland segmentation and quantitation of gland uptake is challenging. We develop a salivary gland SPECT/CT with automated segmentation using a deep convolutional neural network (CNN). The protocol comprises SPECT/CT at 20 min, sialagogue stimulation, and SPECT at 40 min post-injection of Tc-99m pertechnetate (555 MBq). The 40-min SPECT was reconstructed using the 20-min CT after misregistration correction. Manual salivary gland segmentation for %injected dose (%ID) by human experts proved highly reproducible, but took 15 min per scan. An automatic salivary segmentation method was developed using a modified 3D U-Net for end-to-end learning from the human experts (n = 333). The automatic segmentation performed comparably with human experts in voxel-wise comparison (mean Dice similarity coefficient of 0.81 for parotid and 0.79 for submandibular, respectively) and gland %ID correlation (R2 = 0.93 parotid, R2 = 0.95 submandibular) with an operating time less than 1 min. The algorithm generated results that were comparable to the reference data. In conclusion, with the aid of a CNN, we developed a quantitative salivary gland SPECT/CT protocol feasible for clinical applications. The method saves analysis time and manual effort while reducing patients’ radiation exposure.
Ga-NOTA Glu-Urea-Lys (NGUL) is a novel prostate-specific membrane antigen (PSMA)-targeting tracer used for PET/CT imaging. This study aimed to compare performance in the detection of primary and metastatic lesions and to compare biodistribution between 68 Ga-NGUL and 68 Ga-PSMA-11 in the same patients with prostate cancer. Methods: Eleven patients with metastatic prostate cancer were prospectively recruited. The quantitative tracer uptake was determined in normal organs and in primary and metastatic lesions. Results: 68 Ga-NGUL showed significantly lower normal-organ uptake and rapid urinary clearance. The number and sites of detected PSMA-positive primary and metastatic lesions were identical, and no significant quantitative uptake difference was observed. 68 Ga-NGUL showed a relatively lower tumor-to-background ratio than 68 Ga-PSMA-11. Conclusion: In a head-to-head comparison with 68 Ga-PSMA-11, 68 Ga-NGUL showed lower uptake in normal organs and similar performance in detecting PSMA-avid primary and metastatic lesions. 68 Ga-NGUL could be a valuable option for PSMA imaging.
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