細胞療法主要指受損器官的修復或是將器官直接置換。然而此治療法目前的主要困境為缺少器官捐贈者以及有限的捐贈器官。幹細胞的增殖與分化能力使其在作為細胞療法的用途上受到關注。近年來，一些研究已經提出誘導細胞分化並引導幹細胞分化成特定表現型的方法。調節幹細胞分化的常規方法是使用化學誘導法，如生長因子(growth factors)，激素(hormones)或市售誘導培養基(commercial induction medium)。然而，化學誘導法通常具有如低效率，費時或高成本等缺點。本研究的目的為開發製造膠原蛋白微島嶼的技術，以更好地控制細胞表現型。此外，本研究也利用光生物調節法(photobiomodulation)提高細胞分化率。
本研究展示製備特定大小和形狀 (正方形：50×50 μm2，和長方形：120×20 μm2) 的膠原蛋白微島嶼的技術並應用於WJ-MSC幹細胞培養。結果顯示，當WJ-MSC培養於NDM (neurogenic differentiation medium)時，長方形微島嶼上的神經細胞分化率（23.30 ± 0.81 %）比在正方形微島嶼（18.00 ± 1.41 %）上還要更高。另一方面，當培養基為ADM (adipogenic differentiation medium)時，WJ-MSCs在正方形微島嶼（14.90 ± 2.26 %）上的脂肪細胞分化傾向比在長方形微島嶼（6.92 ± 3.07 %）上更高。為了提高細胞分化率，本研究也利用外源性光生物調節法(EPM, extrinsic photobiomodulation)，在幹細胞培養於膠原蛋白微島嶼的同時，加入光敏劑Verteporfin並照射波長為690 nm的激光。結果顯示，在正方形膠原蛋白微島嶼和長方形膠原蛋白微島嶼上使用EPM並以一般培養基進行培養分別可以誘導高比例的脂肪細胞分化（21.5 ± 5.23 %）和神經細胞分化（38.33 ± 10.22 %）。
總結而言，本研究展示EPM技術可在不使用物理或化學的誘導法的同時提升神經細胞或脂肪細胞的分化率。此外，本研究也發展了能製備具備幾何形狀的膠原蛋白微島嶼，並利用微島嶼誘導幹細胞分化表現型。EPM與膠原蛋白微島嶼的結合可以取代傳統的化學因子來增強細胞分化。本研究也有望在未來的實驗中發展出關於細胞選擇性和加速細胞分化為包含體細胞(somatic cells)在內的各種細胞類型的能力。

Cellular therapy is one type of medical treatments that related closely with the restoration or the direct replacement of damaged organs. However, the lack of donors and the limitation of organs were the major problems for the treatments. Stem cells were reported as an alternative for cellular therapy because of the possibility modulability toward proliferation and differentiation. In recent year, several studies have demonstrated the possibilities to induce cell differentiation and to direct stem cells to specific differentiation phenotypes. Conventional method to modulate the stem cell differentiation focused on applying chemical inducing reagents such as growth factors, hormones or commercial induction medium. However, chemical inducing reagent methods usually possessed disadvantages including low efficiency, time consuming, or high-costs. The goals of this research are to develop techniques to prepare arrays of collagen islands with the dimension of micrometer to control the phenotype of stem cells. In addition, the photobiomodulation was also applied to further promote cell differentiation rate.
This study demonstrated the technique to induce the differentiation of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) on collagen microislands with different topological cues which are the square patterns of 50 × 50 μm2 and rectangular patterns of 120 × 20 μm2. By culturing in neurogenic differentiation medium (NDM), WJ-MSCs showed higher neurogenic differentiation on rectangular microislands (23.30 ± 0.81 %) over square microislands (18.00 ± 1.41 %). On the other hand, when the medium was adipogenic differentiation medium (ADM), WJ-MSCs tended to undergo adipogenic differentiation on the square microislands (14.90 ± 2 .26 %) when compared with that on the rectangular microislands (6.92 ± 3.07 %). In order to increase the percentage of cells differentiation, the extrinsic photobiomodulation (EPM) method, applying photosensitizer (verteporfin) and shining the laser light at the wavelength 690 nm, was applied to WJ-MSCs cultured on collagen microislands. General maintenance medium with EPM on square microislands and rectangular microislands can induce high percentage of adipogenic (21.5 ± 5.23 %) and neurogenic differentiation (38.33 ± 10.22 %), respectively.
In conclusion, this study demonstrated that EPM could induce neurogenic and adipogenic differentiation without using chemical or physical cues. Moreover, the collagen microislands with different aspect ratios were successfully developed which can dictate cell differentiation phenotypes. Lastly, the synergistic effects of EPM and the topological cues of collagen arrays can replace the chemical factor to enhance cell differentiation. This work is also promising for future experiments to selection and acceleration of cell differentiation towards various cell types including somatic cells.

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